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T-Cell Development: From T-Lineage Specification to Intrathymic Maturation

  • Kogulan Yoganathan
  • Edward L. Y. Chen
  • Jastaranpreet Singh
  • Juan Carlos Zúñiga-PflückerEmail author
Chapter

Abstract

T-cell development occurs in the thymus in both mice and humans. Upon entry into the thymus, bone marrow-derived blood-borne progenitors receive instructive signals, including Notch signaling, to extinguish their potential to develop into alternative immune lineages while committing to the T-cell fate. Upon T-lineage commitment, developing T-cells receive further instructional cues to generate different T-cell sublineages, which together possess diverse immunological functions to provide host immunity. Over the years, numerous studies have contributed to a greater understanding of key thymic signals that govern T-cell differentiation and subset generation. Here, we review these critical signaling factors that govern the different stages of both mouse and human T-cell development, while also focusing on the transcriptional changes that mediate T-cell identity and diversity.

References

  1. Adams EJ, Gu S, Luoma AM (2015) Human gamma delta T cells: evolution and ligand recognition. Cell Immunol 296:31–40.  https://doi.org/10.1016/j.cellimm.2015.04.008CrossRefPubMedPubMedCentralGoogle Scholar
  2. Adler SH et al (2003) Notch signaling augments T cell responsiveness by enhancing CD25 expression. J Immunol 171:2896–2903PubMedCrossRefPubMedCentralGoogle Scholar
  3. Alonzo ES et al (2010) Development of promyelocytic zinc finger and ThPOK-expressing innate gamma delta T cells is controlled by strength of TCR signaling and Id3. J Immunol 184:1268–1279.  https://doi.org/10.4049/jimmunol.0903218CrossRefPubMedPubMedCentralGoogle Scholar
  4. Anderson MK, Hernandez-Hoyos G, Diamond RA, Rothenberg EV (1999) Precise developmental regulation of Ets family transcription factors during specification and commitment to the T cell lineage. Development 126:3131–3148PubMedPubMedCentralGoogle Scholar
  5. Anderson MK, Weiss AH, Hernandez-Hoyos G, Dionne CJ, Rothenberg EV (2002a) Constitutive expression of PU.1 in fetal hematopoietic progenitors blocks T cell development at the pro-T cell stage. Immunity 16:285–296PubMedCrossRefPubMedCentralGoogle Scholar
  6. Anderson MS et al (2002b) Projection of an immunological self shadow within the thymus by the aire protein. Science 298:1395–1401.  https://doi.org/10.1126/science.1075958CrossRefPubMedPubMedCentralGoogle Scholar
  7. Andersson ER, Sandberg R, Lendahl U (2011) Notch signaling: simplicity in design, versatility in function. Development 138:3593–3612.  https://doi.org/10.1242/dev.063610CrossRefPubMedPubMedCentralGoogle Scholar
  8. Awong G, Herer E, Surh CD, Dick JE, La Motte-Mohs RN, Zuniga-Pflucker JC (2009) Characterization in vitro and engraftment potential in vivo of human progenitor T cells generated from hematopoietic stem cells. Blood 114:972–982.  https://doi.org/10.1182/blood-2008-10-187013CrossRefPubMedPubMedCentralGoogle Scholar
  9. Awong G et al (2013) Human proT-cells generated in vitro facilitate hematopoietic stem cell-derived T-lymphopoiesis in vivo and restore thymic architecture. Blood 122:4210–4219PubMedPubMedCentralCrossRefGoogle Scholar
  10. Baecher-Allan C, Brown JA, Freeman GJ, Hafler DA (2001) CD4+CD25high regulatory cells in human peripheral blood. J Immunol 167:1245–1253PubMedCrossRefPubMedCentralGoogle Scholar
  11. Baev DV, Peng XH, Song L, Barnhart JR, Crooks GM, Weinberg KI, Metelitsa LS (2004) Distinct homeostatic requirements of CD4+ and CD4- subsets of Valpha24-invariant natural killer T cells in humans. Blood 104:4150–4156.  https://doi.org/10.1182/blood-2004-04-1629CrossRefPubMedPubMedCentralGoogle Scholar
  12. Bain G et al (1997) E2A deficiency leads to abnormalities in alphabeta T-cell development and to rapid development of T-cell lymphomas. Mol Cell Biol 17:4782–4791PubMedPubMedCentralCrossRefGoogle Scholar
  13. Bain G, Cravatt CB, Loomans C, Alberola-Ila J, Hedrick SM, Murre C (2001) Regulation of the helix-loop-helix proteins, E2A and Id3, by the Ras-ERK MAPK cascade. Nat Immunol 2:165–171.  https://doi.org/10.1038/84273CrossRefPubMedPubMedCentralGoogle Scholar
  14. Barndt R, Dai MF, Zhuang Y (1999) A novel role for HEB downstream or parallel to the pre-TCR signaling pathway during alpha beta thymopoiesis. J Immunol 163:3331–3343PubMedPubMedCentralGoogle Scholar
  15. Belle I, Zhuang Y (2014) E proteins in lymphocyte development and lymphoid diseases. Curr Top Dev Biol 110:153–187.  https://doi.org/10.1016/B978-0-12-405943-6.00004-XCrossRefPubMedPubMedCentralGoogle Scholar
  16. Bendelac A (1995) Positive selection of mouse NK1+ T cells by CD1-expressing cortical thymocytes. J Exp Med 182:2091–2096PubMedCrossRefPubMedCentralGoogle Scholar
  17. Benezra R, Davis RL, Lockshon D, Turner DL, Weintraub H (1990) The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell 61:49–59PubMedCrossRefPubMedCentralGoogle Scholar
  18. Benlagha K, Wei DG, Veiga J, Teyton L, Bendelac A (2005) Characterization of the early stages of thymic NKT cell development. J Exp Med 202:485–492.  https://doi.org/10.1084/jem.20050456CrossRefPubMedPubMedCentralGoogle Scholar
  19. Bennett CL et al (2001) The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 27:20–21.  https://doi.org/10.1038/83713CrossRefPubMedGoogle Scholar
  20. Beringer DX et al (2015) T cell receptor reversed polarity recognition of a self-antigen major histocompatibility complex. Nat Immunol 16:1153–1161.  https://doi.org/10.1038/ni.3271CrossRefPubMedPubMedCentralGoogle Scholar
  21. Berzins SP, Cochrane AD, Pellicci DG, Smyth MJ, Godfrey DI (2005) Limited correlation between human thymus and blood NKT cell content revealed by an ontogeny study of paired tissue samples. Eur J Immunol 35:1399–1407.  https://doi.org/10.1002/eji.200425958CrossRefPubMedPubMedCentralGoogle Scholar
  22. Blom B, Spits H (2006) Development of human lymphoid cells. Annu Rev Immunol 24:287–320.  https://doi.org/10.1146/annurev.immunol.24.021605.090612CrossRefPubMedPubMedCentralGoogle Scholar
  23. Blom B et al (1999) TCR gene rearrangements and expression of the pre-T cell receptor complex during human T-cell differentiation. Blood 93:3033–3043PubMedPubMedCentralGoogle Scholar
  24. Bonasio R, Scimone ML, Schaerli P, Grabie N, Lichtman AH, von Andrian UH (2006) Clonal deletion of thymocytes by circulating dendritic cells homing to the thymus. Nat Immunol 7:1092–1100.  https://doi.org/10.1038/ni1385CrossRefPubMedPubMedCentralGoogle Scholar
  25. Brauer PM, Singh J, Xhiku S, Zuniga-Pflucker JC (2016) T cell genesis: in vitro veritas est? Trends Immunol 37:889–901.  https://doi.org/10.1016/j.it.2016.09.008CrossRefPubMedPubMedCentralGoogle Scholar
  26. Carding SR, Egan PJ (2002) Gammadelta T cells: functional plasticity and heterogeneity. Nat Rev Immunol 2:336–345.  https://doi.org/10.1038/nri797CrossRefPubMedPubMedCentralGoogle Scholar
  27. Carpenter AC, Bosselut R (2010) Decision checkpoints in the thymus. Nat Immunol 11:666–673.  https://doi.org/10.1038/ni.1887CrossRefPubMedPubMedCentralGoogle Scholar
  28. Carrasco YR, Trigueros C, Ramiro AR, de Yebenes VG, Toribio ML (1999) Beta-selection is associated with the onset of CD8beta chain expression on CD4(+)CD8alphaalpha(+) pre-T cells during human intrathymic development. Blood 94:3491–3498PubMedPubMedCentralGoogle Scholar
  29. Champhekar A, Damle SS, Freedman G, Carotta S, Nutt SL, Rothenberg EV (2015) Regulation of early T-lineage gene expression and developmental progression by the progenitor cell transcription factor PU.1. Genes Dev 29:832–848.  https://doi.org/10.1101/gad.259879.115CrossRefPubMedPubMedCentralGoogle Scholar
  30. Ciofani M, Zuniga-Pflucker JC (2005) Notch promotes survival of pre-T cells at the beta-selection checkpoint by regulating cellular metabolism. Nat Immunol 6:881–888.  https://doi.org/10.1038/ni1234CrossRefPubMedPubMedCentralGoogle Scholar
  31. Ciofani M, Zuniga-Pflucker JC (2007) The thymus as an inductive site for T lymphopoiesis. Annu Rev Cell Dev Biol 23:463–493.  https://doi.org/10.1146/annurev.cellbio.23.090506.123547CrossRefPubMedGoogle Scholar
  32. Ciofani M, Knowles GC, Wiest DL, von Boehmer H, Zuniga-Pflucker JC (2006) Stage-specific and differential notch dependency at the alphabeta and gammadelta T lineage bifurcation. Immunity 25:105–116.  https://doi.org/10.1016/j.immuni.2006.05.010CrossRefPubMedPubMedCentralGoogle Scholar
  33. Coffey F et al (2014) The TCR ligand-inducible expression of CD73 marks gammadelta lineage commitment and a metastable intermediate in effector specification. J Exp Med 211:329–343.  https://doi.org/10.1084/jem.20131540CrossRefPubMedPubMedCentralGoogle Scholar
  34. Cosway EJ et al (2017) Redefining thymus medulla specialization for central tolerance. J Exp Med 214:3183–3195.  https://doi.org/10.1084/jem.20171000CrossRefPubMedPubMedCentralGoogle Scholar
  35. D’Cruz LM, Knell J, Fujimoto JK, Goldrath AW (2010) An essential role for the transcription factor HEB in thymocyte survival, Tcra rearrangement and the development of natural killer T cells. Nat Immunol 11:240–249.  https://doi.org/10.1038/ni.1845CrossRefPubMedPubMedCentralGoogle Scholar
  36. D’Cruz LM, Stradner MH, Yang CY, Goldrath AW (2014) E and Id proteins influence invariant NKT cell sublineage differentiation and proliferation. J Immunol 192:2227–2236.  https://doi.org/10.4049/jimmunol.1302904CrossRefPubMedPubMedCentralGoogle Scholar
  37. Das R, Sant’Angelo DB, Nichols KE (2010) Transcriptional control of invariant NKT cell development. Immunol Rev 238:195–215.  https://doi.org/10.1111/j.1600-065X.2010.00962.xCrossRefPubMedPubMedCentralGoogle Scholar
  38. Das DK et al (2016) Pre-T cell receptors (Pre-TCRs) leverage vbeta complementarity determining regions (CDRs) and hydrophobic patch in mechanosensing thymic self-ligands. J Biol Chem 291:25292–25305.  https://doi.org/10.1074/jbc.M116.752865CrossRefPubMedPubMedCentralGoogle Scholar
  39. Dashtsoodol N et al (2017) Alternative pathway for the development of Valpha14(+) NKT cells directly from CD4(-)CD8(-) thymocytes that bypasses the CD4(+)CD8(+) stage. Nat Immunol 18:274–282.  https://doi.org/10.1038/ni.3668CrossRefPubMedGoogle Scholar
  40. De Obaldia ME et al (2013) T cell development requires constraint of the myeloid regulator C/EBP-alpha by the Notch target and transcriptional repressor Hes1. Nat Immunol 14:1277–1284.  https://doi.org/10.1038/ni.2760CrossRefPubMedPubMedCentralGoogle Scholar
  41. De Smedt M et al (2002) Active form of Notch imposes T cell fate in human progenitor cells. J Immunol 169:3021–3029PubMedCrossRefPubMedCentralGoogle Scholar
  42. De Smedt M, Hoebeke I, Plum J (2004) Human bone marrow CD34+ progenitor cells mature to T cells on OP9-DL1 stromal cell line without thymus microenvironment. Blood Cells Mol Dis 33:227–232.  https://doi.org/10.1016/j.bcmd.2004.08.007CrossRefPubMedPubMedCentralGoogle Scholar
  43. De Smedt M, Hoebeke I, Reynvoet K, Leclercq G, Plum J (2005) Different thresholds of Notch signaling bias human precursor cells toward B-, NK-, monocytic/dendritic-, or T-cell lineage in thymus microenvironment. Blood 106:3498–3506.  https://doi.org/10.1182/blood-2005-02-0496CrossRefPubMedPubMedCentralGoogle Scholar
  44. Deftos ML, Huang E, Ojala EW, Forbush KA, Bevan MJ (2000) Notch1 signaling promotes the maturation of CD4 and CD8 SP thymocytes. Immunity 13:73–84PubMedPubMedCentralCrossRefGoogle Scholar
  45. Del Real MM, Rothenberg EV (2013) Architecture of a lymphomyeloid developmental switch controlled by PU.1, Notch and Gata3. Development 140:1207–1219.  https://doi.org/10.1242/dev.088559CrossRefPubMedPubMedCentralGoogle Scholar
  46. Dellabona P, Padovan E, Casorati G, Brockhaus M, Lanzavecchia A (1994) An invariant V alpha 24-J alpha Q/V beta 11 T cell receptor is expressed in all individuals by clonally expanded CD4-8- T cells. J Exp Med 180:1171–1176PubMedCrossRefPubMedCentralGoogle Scholar
  47. Derbinski J, Schulte A, Kyewski B, Klein L (2001) Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self. Nat Immunol 2:1032–1039.  https://doi.org/10.1038/ni723CrossRefPubMedPubMedCentralGoogle Scholar
  48. Dervovic DD et al (2013) Cellular and molecular requirements for the selection of in vitro-generated CD8 T cells reveal a role for Notch. J Immunol 191:1704–1715.  https://doi.org/10.4049/jimmunol.1300417CrossRefPubMedPubMedCentralGoogle Scholar
  49. Dik WA et al (2005) New insights on human T cell development by quantitative T cell receptor gene rearrangement studies and gene expression profiling. J Exp Med 201:1715–1723.  https://doi.org/10.1084/jem.20042524CrossRefPubMedPubMedCentralGoogle Scholar
  50. Dimova T et al (2015) Effector Vgamma9Vdelta2 T cells dominate the human fetal gammadelta T-cell repertoire. Proc Natl Acad Sci U S A 112:E556–E565.  https://doi.org/10.1073/pnas.1412058112CrossRefPubMedPubMedCentralGoogle Scholar
  51. DiSanto JP, Rieux-Laucat F, Dautry-Varsat A, Fischer A, de Saint Basile G (1994) Defective human interleukin 2 receptor gamma chain in an atypical X chromosome-linked severe combined immunodeficiency with peripheral T cells. Proc Natl Acad Sci U S A 91:9466–9470PubMedPubMedCentralCrossRefGoogle Scholar
  52. Doerfler P, Shearman MS, Perlmutter RM (2001) Presenilin-dependent gamma-secretase activity modulates thymocyte development. Proc Natl Acad Sci U S A 98:9312–9317.  https://doi.org/10.1073/pnas.161102498CrossRefPubMedPubMedCentralGoogle Scholar
  53. Donskoy E, Foss D, Goldschneider I (2003) Gated importation of prothymocytes by adult mouse thymus is coordinated with their periodic mobilization from bone marrow. J Immunol 171:3568–3575PubMedCrossRefPubMedCentralGoogle Scholar
  54. Dontje W et al (2006) Delta-like1-induced Notch1 signaling regulates the human plasmacytoid dendritic cell versus T-cell lineage decision through control of GATA-3 and Spi-B. Blood 107:2446–2452.  https://doi.org/10.1182/blood-2005-05-2090CrossRefPubMedPubMedCentralGoogle Scholar
  55. Doulatov S, Notta F, Eppert K, Nguyen LT, Ohashi PS, Dick JE (2010) Revised map of the human progenitor hierarchy shows the origin of macrophages and dendritic cells in early lymphoid development. Nat Immunol 11:585–593.  https://doi.org/10.1038/ni.1889CrossRefPubMedPubMedCentralGoogle Scholar
  56. Durum SK, Candeias S, Nakajima H, Leonard WJ, Baird AM, Berg LJ, Muegge K (1998) Interleukin 7 receptor control of T cell receptor gamma gene rearrangement: role of receptor-associated chains and locus accessibility. J Exp Med 188:2233–2241PubMedPubMedCentralCrossRefGoogle Scholar
  57. Egawa T, Littman DR (2008) ThPOK acts late in specification of the helper T cell lineage and suppresses Runx-mediated commitment to the cytotoxic T cell lineage. Nat Immunol 9:1131–1139.  https://doi.org/10.1038/ni.1652CrossRefPubMedPubMedCentralGoogle Scholar
  58. Egawa T, Tillman RE, Naoe Y, Taniuchi I, Littman DR (2007) The role of the Runx transcription factors in thymocyte differentiation and in homeostasis of naive T cells. J Exp Med 204:1945–1957.  https://doi.org/10.1084/jem.20070133CrossRefPubMedPubMedCentralGoogle Scholar
  59. Engel I, Murre C (1999) Ectopic expression of E47 or E12 promotes the death of E2A-deficient lymphomas. Proc Natl Acad Sci U S A 96:996–1001PubMedPubMedCentralCrossRefGoogle Scholar
  60. Etzensperger R et al (2017) Identification of lineage-specifying cytokines that signal all CD8(+)-cytotoxic-lineage-fate ‘decisions’ in the thymus. Nat Immunol 18:1218–1227.  https://doi.org/10.1038/ni.3847CrossRefPubMedPubMedCentralGoogle Scholar
  61. Farley AM et al (2013) Dynamics of thymus organogenesis and colonization in early human development. Development 140:2015–2026.  https://doi.org/10.1242/dev.087320CrossRefPubMedPubMedCentralGoogle Scholar
  62. Felices M, Yin CC, Kosaka Y, Kang J, Berg LJ (2009) Tec kinase Itk in gammadeltaT cells is pivotal for controlling IgE production in vivo. Proc Natl Acad Sci U S A 106:8308–8313.  https://doi.org/10.1073/pnas.0808459106CrossRefPubMedPubMedCentralGoogle Scholar
  63. Feyerabend TB et al (2009) Deletion of Notch1 converts pro-T cells to dendritic cells and promotes thymic B cells by cell-extrinsic and cell-intrinsic mechanisms. Immunity 30:67–79.  https://doi.org/10.1016/j.immuni.2008.10.016CrossRefPubMedPubMedCentralGoogle Scholar
  64. Fisher AG, Larsson L, Goff LK, Restall DE, Happerfield L, Merkenschlager M (1990) Human thymocyte development in mouse organ cultures. Int Immunol 2:571–578PubMedCrossRefPubMedCentralGoogle Scholar
  65. Forster R, Davalos-Misslitz AC, Rot A (2008) CCR7 and its ligands: balancing immunity and tolerance. Nat Rev Immunol 8:362–371.  https://doi.org/10.1038/nri2297CrossRefPubMedPubMedCentralGoogle Scholar
  66. Foss DL, Donskoy E, Goldschneider I (2001) The importation of hematogenous precursors by the thymus is a gated phenomenon in normal adult mice. J Exp Med 193:365–374PubMedPubMedCentralCrossRefGoogle Scholar
  67. Fowlkes BJ, Robey EA (2002) A reassessment of the effect of activated Notch1 on CD4 and CD8 T cell development. J Immunol 169:1817–1821PubMedCrossRefPubMedCentralGoogle Scholar
  68. Fry TJ, Mackall CL (2002) Current concepts of thymic aging. Springer Semin Immunopathol 24:7–22PubMedCrossRefPubMedCentralGoogle Scholar
  69. Gallegos AM, Bevan MJ (2004) Central tolerance to tissue-specific antigens mediated by direct and indirect antigen presentation. J Exp Med 200:1039–1049.  https://doi.org/10.1084/jem.20041457CrossRefPubMedPubMedCentralGoogle Scholar
  70. Galy A, Verma S, Barcena A, Spits H (1993) Precursors of CD3+CD4+CD8+ cells in the human thymus are defined by expression of CD34. Delineation of early events in human thymic development. J Exp Med 178:391–401PubMedCrossRefPubMedCentralGoogle Scholar
  71. Galy A, Travis M, Cen D, Chen B (1995) Human T, B, natural killer, and dendritic cells arise from a common bone marrow progenitor cell subset. Immunity 3:459–473PubMedCrossRefPubMedCentralGoogle Scholar
  72. Gapin L (2016) Development of invariant natural killer T cells. Curr Opin Immunol 39:68–74.  https://doi.org/10.1016/j.coi.2016.01.001CrossRefPubMedPubMedCentralGoogle Scholar
  73. Garbe AI, Krueger A, Gounari F, Zuniga-Pflucker JC, von Boehmer H (2006) Differential synergy of Notch and T cell receptor signaling determines alphabeta versus gammadelta lineage fate. J Exp Med 203:1579–1590.  https://doi.org/10.1084/jem.20060474CrossRefPubMedPubMedCentralGoogle Scholar
  74. Garcia-Leon MJ, Fuentes P, de la Pompa JL, Toribio ML (2018) Dynamic regulation of Notch1 activation and Notch ligand expression in human thymus development. Development 145:pii: dev165597.  https://doi.org/10.1242/dev.165597CrossRefGoogle Scholar
  75. Garcia-Ojeda ME et al (2013) GATA-3 promotes T-cell specification by repressing B-cell potential in pro-T cells in mice. Blood 121:1749–1759.  https://doi.org/10.1182/blood-2012-06-440065CrossRefPubMedPubMedCentralGoogle Scholar
  76. Garcia-Peydro M, de Yebenes VG, Toribio ML (2003) Sustained Notch1 signaling instructs the earliest human intrathymic precursors to adopt a gammadelta T-cell fate in fetal thymus organ culture. Blood 102:2444–2451.  https://doi.org/10.1182/blood-2002-10-3261CrossRefPubMedPubMedCentralGoogle Scholar
  77. Georgescu C et al (2008) A gene regulatory network armature for T lymphocyte specification. Proc Natl Acad Sci U S A 105:20100–20105.  https://doi.org/10.1073/pnas.0806501105CrossRefPubMedPubMedCentralGoogle Scholar
  78. Germar K et al (2011) T-cell factor 1 is a gatekeeper for T-cell specification in response to Notch signaling. Proc Natl Acad Sci U S A 108:20060–20065.  https://doi.org/10.1073/pnas.1110230108CrossRefPubMedPubMedCentralGoogle Scholar
  79. Gherardin NA et al (2018) Human blood MAIT cell subsets defined using MR1 tetramers. Immunol Cell Biol 96:507–525.  https://doi.org/10.1111/imcb.12021CrossRefPubMedPubMedCentralGoogle Scholar
  80. Ghisi M et al (2011) Modulation of microRNA expression in human T-cell development: targeting of NOTCH3 by miR-150. Blood 117:7053–7062.  https://doi.org/10.1182/blood-2010-12-326629CrossRefPubMedPubMedCentralGoogle Scholar
  81. Ghosh JK, Romanow WJ, Murre C (2001) Induction of a diverse T cell receptor gamma/delta repertoire by the helix-loop-helix proteins E2A and HEB in nonlymphoid cells. J Exp Med 193:769–776PubMedPubMedCentralCrossRefGoogle Scholar
  82. Godfrey DI, MacDonald HR, Kronenberg M, Smyth MJ, Van Kaer L (2004) NKT cells: what’s in a name? Nat Rev Immunol 4:231–237.  https://doi.org/10.1038/nri1309CrossRefPubMedPubMedCentralGoogle Scholar
  83. Goldschneider I, Komschlies KL, Greiner DL (1986) Studies of thymocytopoiesis in rats and mice. I. Kinetics of appearance of thymocytes using a direct intrathymic adoptive transfer assay for thymocyte precursors. J Exp Med 163:1–17PubMedCrossRefPubMedCentralGoogle Scholar
  84. Goronzy JJ, Weyand CM (2005) T cell development and receptor diversity during aging. Curr Opin Immunol 17:468–475.  https://doi.org/10.1016/j.coi.2005.07.020CrossRefPubMedPubMedCentralGoogle Scholar
  85. Haddad R et al (2006) Dynamics of thymus-colonizing cells during human development. Immunity 24:217–230PubMedCrossRefPubMedCentralGoogle Scholar
  86. Hadeiba H, Butcher EC (2013) Thymus-homing dendritic cells in central tolerance. Eur J Immunol 43:1425–1429.  https://doi.org/10.1002/eji.201243192CrossRefPubMedPubMedCentralGoogle Scholar
  87. Hadland BK et al (2001) Gamma -secretase inhibitors repress thymocyte development. Proc Natl Acad Sci U S A 98:7487–7491.  https://doi.org/10.1073/pnas.131202798CrossRefPubMedPubMedCentralGoogle Scholar
  88. Haks MC et al (2005) Attenuation of gammadeltaTCR signaling efficiently diverts thymocytes to the alphabeta lineage. Immunity 22:595–606.  https://doi.org/10.1016/j.immuni.2005.04.003CrossRefPubMedPubMedCentralGoogle Scholar
  89. Hamann A, Klugewitz K, Austrup F, Jablonski-Westrich D (2000) Activation induces rapid and profound alterations in the trafficking of T cells. Eur J Immunol 30:3207–3218.  https://doi.org/10.1002/1521-4141(200011)30:11<3207::AID-IMMU3207>3.0.CO;2-LCrossRefPubMedPubMedCentralGoogle Scholar
  90. Hanabuchi S et al (2010) Thymic stromal lymphopoietin-activated plasmacytoid dendritic cells induce the generation of FOXP3+ regulatory T cells in human thymus. J Immunol 184:2999–3007.  https://doi.org/10.4049/jimmunol.0804106CrossRefPubMedPubMedCentralGoogle Scholar
  91. Hao QL et al (2008) Human intrathymic lineage commitment is marked by differential CD7 expression: identification of CD7- lympho-myeloid thymic progenitors. Blood 111:1318–1326PubMedPubMedCentralCrossRefGoogle Scholar
  92. Havran WL, Allison JP (1990) Origin of Thy-1+ dendritic epidermal cells of adult mice from fetal thymic precursors. Nature 344:68–70.  https://doi.org/10.1038/344068a0CrossRefPubMedPubMedCentralGoogle Scholar
  93. Hayes SM, Li L, Love PE (2005) TCR signal strength influences alphabeta/gammadelta lineage fate. Immunity 22:583–593.  https://doi.org/10.1016/j.immuni.2005.03.014CrossRefPubMedPubMedCentralGoogle Scholar
  94. Haynes BF, Martin ME, Kay HH, Kurtzberg J (1988) Early events in human T cell ontogeny. Phenotypic characterization and immunohistologic localization of T cell precursors in early human fetal tissues. J Exp Med 168:1061–1080PubMedCrossRefPubMedCentralGoogle Scholar
  95. Heemskerk MH et al (1997) Inhibition of T cell and promotion of natural killer cell development by the dominant negative helix loop helix factor Id3. J Exp Med 186:1597–1602PubMedPubMedCentralCrossRefGoogle Scholar
  96. Ho IC, Tai TS, Pai SY (2009) GATA3 and the T-cell lineage: essential functions before and after T-helper-2-cell differentiation. Nat Rev Immunol 9:125–135.  https://doi.org/10.1038/nri2476CrossRefPubMedPubMedCentralGoogle Scholar
  97. Hoebeke I, De Smedt M, Stolz F, Pike-Overzet K, Staal FJ, Plum J, Leclercq G (2007) T-, B- and NK-lymphoid, but not myeloid cells arise from human CD34(+)CD38(-)CD7(+) common lymphoid progenitors expressing lymphoid-specific genes. Leukemia 21:311–319.  https://doi.org/10.1038/sj.leu.2404488CrossRefPubMedPubMedCentralGoogle Scholar
  98. Holmes R, Zuniga-Pflucker JC (2009) The OP9-DL1 system: generation of T-lymphocytes from embryonic or hematopoietic stem cells in vitro. Cold Spring Harb Protoc 2009:pdb prot5156.  https://doi.org/10.1101/pdb.prot5156CrossRefPubMedPubMedCentralGoogle Scholar
  99. Hozumi K et al (2008) Delta-like 4 is indispensable in thymic environment specific for T cell development. J Exp Med 205:2507–2513.  https://doi.org/10.1084/jem.20080134CrossRefPubMedPubMedCentralGoogle Scholar
  100. Hsu HL et al (1994) Preferred sequences for DNA recognition by the TAL1 helix-loop-helix proteins. Mol Cell Biol 14:1256–1265PubMedPubMedCentralCrossRefGoogle Scholar
  101. Hsu LY, Lauring J, Liang HE, Greenbaum S, Cado D, Zhuang Y, Schlissel MS (2003) A conserved transcriptional enhancer regulates RAG gene expression in developing B cells. Immunity 19:105–117PubMedCrossRefPubMedCentralGoogle Scholar
  102. Hu JS, Olson EN, Kingston RE (1992) HEB, a helix-loop-helix protein related to E2A and ITF2 that can modulate the DNA-binding ability of myogenic regulatory factors. Mol Cell Biol 12:1031–1042PubMedPubMedCentralCrossRefGoogle Scholar
  103. Hu T et al (2013) Increased level of E protein activity during invariant NKT development promotes differentiation of invariant NKT2 and invariant NKT17 subsets. J Immunol 191:5065–5073.  https://doi.org/10.4049/jimmunol.1301546CrossRefPubMedPubMedCentralGoogle Scholar
  104. Huang C, Kanagawa O (2001) Ordered and coordinated rearrangement of the TCR alpha locus: role of secondary rearrangement in thymic selection. J Immunol 166:2597–2601PubMedCrossRefPubMedCentralGoogle Scholar
  105. Huang YH, Li D, Winoto A, Robey EA (2004) Distinct transcriptional programs in thymocytes responding to T cell receptor, Notch, and positive selection signals. Proc Natl Acad Sci U S A 101:4936–4941.  https://doi.org/10.1073/pnas.0401133101CrossRefPubMedPubMedCentralGoogle Scholar
  106. Ikawa T, Fujimoto S, Kawamoto H, Katsura Y, Yokota Y (2001) Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2. Proc Natl Acad Sci U S A 98:5164–5169.  https://doi.org/10.1073/pnas.091537598CrossRefPubMedPubMedCentralGoogle Scholar
  107. Ikawa T et al (2010) An essential developmental checkpoint for production of the T cell lineage. Science 329:93–96.  https://doi.org/10.1126/science.1188995CrossRefPubMedPubMedCentralGoogle Scholar
  108. In TSH et al (2017) HEB is required for the specification of fetal IL-17-producing gammadelta T cells. Nat Commun 8:2004.  https://doi.org/10.1038/s41467-017-02225-5CrossRefPubMedPubMedCentralGoogle Scholar
  109. Irving BA, Alt FW, Killeen N (1998) Thymocyte development in the absence of pre-T cell receptor extracellular immunoglobulin domains. Science 280:905–908PubMedCrossRefPubMedCentralGoogle Scholar
  110. Isoda T et al (2017) Non-coding transcription instructs chromatin folding and compartmentalization to dictate enhancer-promoter communication and T cell fate. Cell 171:103–119 e118.  https://doi.org/10.1016/j.cell.2017.09.001CrossRefPubMedPubMedCentralGoogle Scholar
  111. Ito K, Van Kaer L, Bonneville M, Hsu S, Murphy DB, Tonegawa S (1990) Recognition of the product of a novel MHC TL region gene (27b) by a mouse gamma delta T cell receptor. Cell 62:549–561PubMedCrossRefPubMedCentralGoogle Scholar
  112. Ito T et al (2008) Two functional subsets of FOXP3+ regulatory T cells in human thymus and periphery. Immunity 28:870–880.  https://doi.org/10.1016/j.immuni.2008.03.018CrossRefPubMedPubMedCentralGoogle Scholar
  113. Izon DJ et al (2001) Notch1 regulates maturation of CD4+ and CD8+ thymocytes by modulating TCR signal strength. Immunity 14:253–264PubMedCrossRefPubMedCentralGoogle Scholar
  114. Jaleco AC et al (2001) Differential effects of Notch ligands Delta-1 and Jagged-1 in human lymphoid differentiation. J Exp Med 194:991–1002PubMedPubMedCentralCrossRefGoogle Scholar
  115. Jensen KD et al (2008) Thymic selection determines gammadelta T cell effector fate: antigen-naive cells make interleukin-17 and antigen-experienced cells make interferon gamma. Immunity 29:90–100.  https://doi.org/10.1016/j.immuni.2008.04.022CrossRefPubMedPubMedCentralGoogle Scholar
  116. Jia J, Dai M, Zhuang Y (2008) E proteins are required to activate germline transcription of the TCR Vbeta8.2 gene. Eur J Immunol 38:2806–2820.  https://doi.org/10.1002/eji.200838144CrossRefPubMedPubMedCentralGoogle Scholar
  117. Joachims ML, Chain JL, Hooker SW, Knott-Craig CJ, Thompson LF (2006) Human alpha beta and gamma delta thymocyte development: TCR gene rearrangements, intracellular TCR beta expression, and gamma delta developmental potential--differences between men and mice. J Immunol 176:1543–1552PubMedPubMedCentralCrossRefGoogle Scholar
  118. Kappes DJ, He X, He X (2006) Role of the transcription factor Th-POK in CD4:CD8 lineage commitment. Immunol Rev 209:237–252.  https://doi.org/10.1111/j.0105-2896.2006.00344.xCrossRefPubMedPubMedCentralGoogle Scholar
  119. Kee BL (2009) E and ID proteins branch out. Nat Rev Immunol 9:175–184.  https://doi.org/10.1038/nri2507CrossRefPubMedPubMedCentralGoogle Scholar
  120. Kim ST et al (2009) The alphabeta T cell receptor is an anisotropic mechanosensor. J Biol Chem 284:31028–31037.  https://doi.org/10.1074/jbc.M109.052712CrossRefPubMedPubMedCentralGoogle Scholar
  121. Klein F et al (2003) T lymphoid differentiation in human bone marrow. Proc Natl Acad Sci U S A 100:6747–6752.  https://doi.org/10.1073/pnas.1031503100CrossRefPubMedPubMedCentralGoogle Scholar
  122. Koch U et al (2008) Delta-like 4 is the essential, nonredundant ligand for Notch1 during thymic T cell lineage commitment. J Exp Med 205:2515–2523.  https://doi.org/10.1084/jem.20080829CrossRefPubMedPubMedCentralGoogle Scholar
  123. Kohu K et al (2005) Overexpression of the Runx3 transcription factor increases the proportion of mature thymocytes of the CD8 single-positive lineage. J Immunol 174:2627–2636PubMedCrossRefPubMedCentralGoogle Scholar
  124. Kondo M, Weissman IL, Akashi K (1997) Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 91:661–672PubMedCrossRefPubMedCentralGoogle Scholar
  125. Kovall RA (2007) Structures of CSL, Notch and Mastermind proteins: piecing together an active transcription complex. Curr Opin Struct Biol 17:117–127.  https://doi.org/10.1016/j.sbi.2006.11.004CrossRefPubMedPubMedCentralGoogle Scholar
  126. Kraft DL, Weissman IL, Waller EK (1993) Differentiation of CD3-4-8- human fetal thymocytes in vivo: characterization of a CD3-4+8- intermediate. J Exp Med 178:265–277PubMedCrossRefPubMedCentralGoogle Scholar
  127. Krueger A, Garbe AI, von Boehmer H (2006) Phenotypic plasticity of T cell progenitors upon exposure to Notch ligands. J Exp Med 203:1977–1984.  https://doi.org/10.1084/jem.20060731CrossRefPubMedPubMedCentralGoogle Scholar
  128. Krueger A, Willenzon S, Lyszkiewicz M, Kremmer E, Forster R (2010) CC chemokine receptor 7 and 9 double-deficient hematopoietic progenitors are severely impaired in seeding the adult thymus. Blood 115:1906–1912.  https://doi.org/10.1182/blood-2009-07-235721CrossRefPubMedPubMedCentralGoogle Scholar
  129. Kurtzberg J, Denning SM, Nycum LM, Singer KH, Haynes BF (1989) Immature human thymocytes can be driven to differentiate into nonlymphoid lineages by cytokines from thymic epithelial cells. Proc Natl Acad Sci U S A 86:7575–7579PubMedPubMedCentralCrossRefGoogle Scholar
  130. La Motte-Mohs RN, Herer E, Zuniga-Pflucker JC (2005) Induction of T-cell development from human cord blood hematopoietic stem cells by Delta-like 1 in vitro. Blood 105:1431–1439.  https://doi.org/10.1182/blood-2004-04-1293CrossRefPubMedPubMedCentralGoogle Scholar
  131. Lai AY, Kondo M (2007) Identification of a bone marrow precursor of the earliest thymocytes in adult mouse. Proc Natl Acad Sci U S A 104:6311–6316.  https://doi.org/10.1073/pnas.0609608104CrossRefPubMedPubMedCentralGoogle Scholar
  132. Laky K, Fowlkes BJ (2007) Presenilins regulate alphabeta T cell development by modulating TCR signaling. J Exp Med 204:2115–2129.  https://doi.org/10.1084/jem.20070550CrossRefPubMedPubMedCentralGoogle Scholar
  133. Laky K, Evans S, Perez-Diez A, Fowlkes BJ (2015) Notch signaling regulates antigen sensitivity of naive CD4+ T cells by tuning co-stimulation. Immunity 42:80–94.  https://doi.org/10.1016/j.immuni.2014.12.027CrossRefPubMedPubMedCentralGoogle Scholar
  134. Langerak AW, Wolvers-Tettero IL, van Gastel-Mol EJ, Oud ME, van Dongen JJ (2001) Basic helix-loop-helix proteins E2A and HEB induce immature T-cell receptor rearrangements in nonlymphoid cells. Blood 98:2456–2465PubMedCrossRefPubMedCentralGoogle Scholar
  135. Lantz O, Bendelac A (1994) An invariant T cell receptor alpha chain is used by a unique subset of major histocompatibility complex class I-specific CD4+ and CD4-8- T cells in mice and humans. J Exp Med 180:1097–1106PubMedCrossRefGoogle Scholar
  136. Lauritsen JP et al (2009) Marked induction of the helix-loop-helix protein Id3 promotes the gammadelta T cell fate and renders their functional maturation Notch independent. Immunity 31:565–575.  https://doi.org/10.1016/j.immuni.2009.07.010CrossRefPubMedPubMedCentralGoogle Scholar
  137. Le Bourhis L, Guerri L, Dusseaux M, Martin E, Soudais C, Lantz O (2011) Mucosal-associated invariant T cells: unconventional development and function. Trends Immunol 32:212–218.  https://doi.org/10.1016/j.it.2011.02.005CrossRefPubMedGoogle Scholar
  138. Lee HM, Hsieh CS (2009) Rare development of Foxp3+ thymocytes in the CD4+CD8+ subset. J Immunol 183:2261–2266.  https://doi.org/10.4049/jimmunol.0901304CrossRefPubMedPubMedCentralGoogle Scholar
  139. Lee W, Lee GR (2018) Transcriptional regulation and development of regulatory T cells. Exp Mol Med 50:e456.  https://doi.org/10.1038/emm.2017.313CrossRefPubMedPubMedCentralGoogle Scholar
  140. Lee SY et al (2014) Noncanonical mode of ERK action controls alternative alphabeta and gammadelta T cell lineage fates. Immunity 41:934–946.  https://doi.org/10.1016/j.immuni.2014.10.021CrossRefPubMedPubMedCentralGoogle Scholar
  141. Lepore M et al (2014) Parallel T-cell cloning and deep sequencing of human MAIT cells reveal stable oligoclonal TCRbeta repertoire. Nat Commun 5:3866.  https://doi.org/10.1038/ncomms4866CrossRefPubMedGoogle Scholar
  142. Leventhal DS et al (2016) Dendritic cells coordinate the development and homeostasis of organ-specific regulatory T cells. Immunity 44:847–859.  https://doi.org/10.1016/j.immuni.2016.01.025CrossRefPubMedPubMedCentralGoogle Scholar
  143. Li L, Leid M, Rothenberg EV (2010a) An early T cell lineage commitment checkpoint dependent on the transcription factor Bcl11b. Science 329:89–93.  https://doi.org/10.1126/science.1188989CrossRefPubMedPubMedCentralGoogle Scholar
  144. Li P et al (2010b) Reprogramming of T cells to natural killer-like cells upon Bcl11b deletion. Science 329:85–89.  https://doi.org/10.1126/science.1188063CrossRefPubMedPubMedCentralGoogle Scholar
  145. Li Y, Brauer PM, Singh J, Xhiku S, Yoganathan K, Zuniga-Pflucker JC, Anderson MK (2017) Targeted disruption of TCF12 reveals HEB as essential in human mesodermal specification and hematopoiesis. Stem Cell Rep 9:779–795.  https://doi.org/10.1016/j.stemcr.2017.07.011CrossRefGoogle Scholar
  146. Lin H, Nieda M, Nicol AJ (2004) Differential proliferative response of NKT cell subpopulations to in vitro stimulation in presence of different cytokines. Eur J Immunol 34:2664–2671.  https://doi.org/10.1002/eji.200324834CrossRefPubMedGoogle Scholar
  147. Lin H, Nieda M, Hutton JF, Rozenkov V, Nicol AJ (2006) Comparative gene expression analysis of NKT cell subpopulations. J Leukoc Biol 80:164–173.  https://doi.org/10.1189/jlb.0705421CrossRefPubMedGoogle Scholar
  148. Lio CW, Hsieh CS (2008) A two-step process for thymic regulatory T cell development. Immunity 28:100–111.  https://doi.org/10.1016/j.immuni.2007.11.021CrossRefPubMedPubMedCentralGoogle Scholar
  149. Liu J, Sato C, Cerletti M, Wagers A (2010) Notch signaling in the regulation of stem cell self-renewal and differentiation. Curr Top Dev Biol 92:367–409.  https://doi.org/10.1016/S0070-2153(10)92012-7CrossRefPubMedGoogle Scholar
  150. Lohr J, Knoechel B, Kahn EC, Abbas AK (2004) Role of B7 in T cell tolerance. J Immunol 173:5028–5035PubMedCrossRefGoogle Scholar
  151. Longabaugh WJR et al (2017) Bcl11b and combinatorial resolution of cell fate in the T-cell gene regulatory network. Proc Natl Acad Sci U S A 114:5800–5807.  https://doi.org/10.1073/pnas.1610617114CrossRefPubMedPubMedCentralGoogle Scholar
  152. Luckey MA, Kimura MY, Waickman AT, Feigenbaum L, Singer A, Park JH (2014) The transcription factor ThPOK suppresses Runx3 and imposes CD4(+) lineage fate by inducing the SOCS suppressors of cytokine signaling. Nat Immunol 15:638–645.  https://doi.org/10.1038/ni.2917CrossRefPubMedPubMedCentralGoogle Scholar
  153. Mackall CL, Gress RE (1997) Thymic aging and T-cell regeneration. Immunol Rev 160:91–102PubMedCrossRefGoogle Scholar
  154. Maillard I et al (2006) The requirement for Notch signaling at the beta-selection checkpoint in vivo is absolute and independent of the pre-T cell receptor. J Exp Med 203:2239–2245.  https://doi.org/10.1084/jem.20061020CrossRefPubMedPubMedCentralGoogle Scholar
  155. Maki K, Sunaga S, Ikuta K (1996) The V-J recombination of T cell receptor-gamma genes is blocked in interleukin-7 receptor-deficient mice. J Exp Med 184:2423–2427PubMedPubMedCentralCrossRefGoogle Scholar
  156. Malhotra N et al (2013) A network of high-mobility group box transcription factors programs innate interleukin-17 production. Immunity 38:681–693.  https://doi.org/10.1016/j.immuni.2013.01.010CrossRefPubMedGoogle Scholar
  157. Malhotra D et al (2016) Tolerance is established in polyclonal CD4(+) T cells by distinct mechanisms, according to self-peptide expression patterns. Nat Immunol 17:187–195.  https://doi.org/10.1038/ni.3327CrossRefPubMedPubMedCentralGoogle Scholar
  158. Manesso E, Chickarmane V, Kueh HY, Rothenberg EV, Peterson C (2013) Computational modelling of T-cell formation kinetics: output regulated by initial proliferation-linked deferral of developmental competence. J R Soc Interface 10:20120774.  https://doi.org/10.1098/rsif.2012.0774CrossRefPubMedPubMedCentralGoogle Scholar
  159. Martin E et al (2009) Stepwise development of MAIT cells in mouse and human. PLoS Biol 7:e54.  https://doi.org/10.1371/journal.pbio.1000054CrossRefPubMedGoogle Scholar
  160. Mbongue J, Nicholas D, Firek A, Langridge W (2014) The role of dendritic cells in tissue-specific autoimmunity. J Immunol Res 2014:857143.  https://doi.org/10.1155/2014/857143CrossRefPubMedPubMedCentralGoogle Scholar
  161. Michie AM, Zuniga-Pflucker JC (2002) Regulation of thymocyte differentiation: pre-TCR signals and beta-selection. Semin Immunol 14:311–323PubMedCrossRefGoogle Scholar
  162. Mohtashami M, Shah DK, Nakase H, Kianizad K, Petrie HT, Zuniga-Pflucker JC (2010) Direct comparison of Dll1- and Dll4-mediated Notch activation levels shows differential lymphomyeloid lineage commitment outcomes. J Immunol 185:867–876.  https://doi.org/10.4049/jimmunol.1000782CrossRefPubMedGoogle Scholar
  163. Moran AE, Holzapfel KL, Xing Y, Cunningham NR, Maltzman JS, Punt J, Hogquist KA (2011) T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse. J Exp Med 208:1279–1289.  https://doi.org/10.1084/jem.20110308CrossRefPubMedPubMedCentralGoogle Scholar
  164. Morita CT, Mariuzza RA, Brenner MB (2000) Antigen recognition by human gamma delta T cells: pattern recognition by the adaptive immune system. Springer Semin Immunopathol 22:191–217PubMedCrossRefGoogle Scholar
  165. Muroi S et al (2008) Cascading suppression of transcriptional silencers by ThPOK seals helper T cell fate. Nat Immunol 9:1113–1121.  https://doi.org/10.1038/ni.1650CrossRefPubMedGoogle Scholar
  166. Naito T, Taniuchi I (2010) The network of transcription factors that underlie the CD4 versus CD8 lineage decision. Int Immunol 22:791–796.  https://doi.org/10.1093/intimm/dxq436CrossRefPubMedGoogle Scholar
  167. Nie L, Xu M, Vladimirova A, Sun XH (2003) Notch-induced E2A ubiquitination and degradation are controlled by MAP kinase activities. EMBO J 22:5780–5792.  https://doi.org/10.1093/emboj/cdg567CrossRefPubMedPubMedCentralGoogle Scholar
  168. Nie L, Zhao Y, Wu W, Yang YZ, Wang HC, Sun XH (2011) Notch-induced Asb2 expression promotes protein ubiquitination by forming non-canonical E3 ligase complexes. Cell Res 21:754–769.  https://doi.org/10.1038/cr.2010.165CrossRefPubMedGoogle Scholar
  169. Nitta T et al (2015) The thymic cortical epithelium determines the TCR repertoire of IL-17-producing gammadeltaT cells. EMBO Rep 16:638–653.  https://doi.org/10.15252/embr.201540096CrossRefPubMedPubMedCentralGoogle Scholar
  170. Nosaka T et al (1995) Defective lymphoid development in mice lacking Jak3. Science 270:800–802PubMedCrossRefGoogle Scholar
  171. Offner F, Van Beneden K, Debacker V, Vanhecke D, Vandekerckhove B, Plum J, Leclercq G (1997) Phenotypic and functional maturation of TCR gammadelta cells in the human thymus. J Immunol 158:4634–4641PubMedGoogle Scholar
  172. Okamoto Y, Douek DC, McFarland RD, Koup RA (2002) Effects of exogenous interleukin-7 on human thymus function. Blood 99:2851–2858PubMedCrossRefGoogle Scholar
  173. Palaga T, Miele L, Golde TE, Osborne BA (2003) TCR-mediated Notch signaling regulates proliferation and IFN-gamma production in peripheral T cells. J Immunol 171:3019–3024PubMedCrossRefGoogle Scholar
  174. Park K, He X, Lee HO, Hua X, Li Y, Wiest D, Kappes DJ (2010) TCR-mediated ThPOK induction promotes development of mature (CD24-) gammadelta thymocytes. EMBO J 29:2329–2341.  https://doi.org/10.1038/emboj.2010.113CrossRefPubMedPubMedCentralGoogle Scholar
  175. Paust S, Lu L, McCarty N, Cantor H (2004) Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease. Proc Natl Acad Sci U S A 101:10398–10403.  https://doi.org/10.1073/pnas.0403342101CrossRefPubMedPubMedCentralGoogle Scholar
  176. Payne KJ, Crooks GM (2002) Human hematopoietic lineage commitment. Immunol Rev 187:48–64PubMedCrossRefPubMedCentralGoogle Scholar
  177. Perry SS, Wang H, Pierce LJ, Yang AM, Tsai S, Spangrude GJ (2004) L-selectin defines a bone marrow analog to the thymic early T-lineage progenitor. Blood 103:2990–2996.  https://doi.org/10.1182/blood-2003-09-3030CrossRefPubMedPubMedCentralGoogle Scholar
  178. Peschon JJ et al (1994) Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J Exp Med 180:1955–1960PubMedCrossRefPubMedCentralGoogle Scholar
  179. Petrie HT, Zuniga-Pflucker JC (2007) Zoned out: functional mapping of stromal signaling microenvironments in the thymus. Annu Rev Immunol 25:649–679.  https://doi.org/10.1146/annurev.immunol.23.021704.115715CrossRefPubMedPubMedCentralGoogle Scholar
  180. Porcelli S, Yockey CE, Brenner MB, Balk SP (1993) Analysis of T cell antigen receptor (TCR) expression by human peripheral blood CD4-8- alpha/beta T cells demonstrates preferential use of several V beta genes and an invariant TCR alpha chain. J Exp Med 178:1–16PubMedCrossRefPubMedCentralGoogle Scholar
  181. Porritt HE, Rumfelt LL, Tabrizifard S, Schmitt TM, Zuniga-Pflucker JC, Petrie HT (2004) Heterogeneity among DN1 prothymocytes reveals multiple progenitors with different capacities to generate T cell and non-T cell lineages. Immunity 20:735–745.  https://doi.org/10.1016/j.immuni.2004.05.004CrossRefPubMedPubMedCentralGoogle Scholar
  182. Prinz I, Silva-Santos B, Pennington DJ (2013) Functional development of gammadelta T cells. Eur J Immunol 43:1988–1994.  https://doi.org/10.1002/eji.201343759CrossRefPubMedPubMedCentralGoogle Scholar
  183. Proietto AI et al (2008) Dendritic cells in the thymus contribute to T-regulatory cell induction. Proc Natl Acad Sci U S A 105:19869–19874.  https://doi.org/10.1073/pnas.0810268105CrossRefPubMedPubMedCentralGoogle Scholar
  184. Pui JC et al (1999) Notch1 expression in early lymphopoiesis influences B versus T lineage determination. Immunity 11:299–308PubMedCrossRefPubMedCentralGoogle Scholar
  185. Qi Q, Xia M, Hu J, Hicks E, Iyer A, Xiong N, August A (2009) Enhanced development of CD4+ gammadelta T cells in the absence of Itk results in elevated IgE production. Blood 114:564–571.  https://doi.org/10.1182/blood-2008-12-196345CrossRefPubMedPubMedCentralGoogle Scholar
  186. Radtke F, Wilson A, Stark G, Bauer M, van Meerwijk J, MacDonald HR, Aguet M (1999) Deficient T cell fate specification in mice with an induced inactivation of Notch1. Immunity 10:547–558PubMedCrossRefPubMedCentralGoogle Scholar
  187. Rahimpour A et al (2015) Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers. J Exp Med 212:1095–1108.  https://doi.org/10.1084/jem.20142110CrossRefPubMedPubMedCentralGoogle Scholar
  188. Ramiro AR, Trigueros C, Marquez C, San Millan JL, Toribio ML (1996) Regulation of pre-T cell receptor (pT alpha-TCR beta) gene expression during human thymic development. J Exp Med 184:519–530PubMedCrossRefPubMedCentralGoogle Scholar
  189. Ramond C et al (2014) Two waves of distinct hematopoietic progenitor cells colonize the fetal thymus. Nat Immunol 15:27–35.  https://doi.org/10.1038/ni.2782CrossRefPubMedPubMedCentralGoogle Scholar
  190. Reimann C et al (2012) Human T-lymphoid progenitors generated in a feeder-cell-free Delta-like-4 culture system promote T-cell reconstitution in NOD/SCID/gammac(-/-) mice. Stem Cells 30:1771–1780.  https://doi.org/10.1002/stem.1145CrossRefPubMedPubMedCentralGoogle Scholar
  191. Rivera RR, Johns CP, Quan J, Johnson RS, Murre C (2000) Thymocyte selection is regulated by the helix-loop-helix inhibitor protein, Id3. Immunity 12:17–26PubMedCrossRefPubMedCentralGoogle Scholar
  192. Roberts NA et al (2012) Rank signaling links the development of invariant gammadelta T cell progenitors and aire(+) medullary epithelium. Immunity 36:427–437.  https://doi.org/10.1016/j.immuni.2012.01.016CrossRefPubMedPubMedCentralGoogle Scholar
  193. Robey E et al (1996) An activated form of Notch influences the choice between CD4 and CD8 T cell lineages. Cell 87:483–492PubMedCrossRefPubMedCentralGoogle Scholar
  194. Rodewald HR, Ogawa M, Haller C, Waskow C, DiSanto JP (1997) Pro-thymocyte expansion by c-kit and the common cytokine receptor gamma chain is essential for repertoire formation. Immunity 6:265–272PubMedCrossRefPubMedCentralGoogle Scholar
  195. Roncarolo MG, Gregori S (2008) Is FOXP3 a bona fide marker for human regulatory T cells? Eur J Immunol 38:925–927.  https://doi.org/10.1002/eji.200838168CrossRefPubMedPubMedCentralGoogle Scholar
  196. Rossi FM et al (2005) Recruitment of adult thymic progenitors is regulated by P-selectin and its ligand PSGL-1. Nat Immunol 6:626–634.  https://doi.org/10.1038/ni1203CrossRefPubMedPubMedCentralGoogle Scholar
  197. Rothenberg EV (2014) Transcriptional control of early T and B cell developmental choices. Annu Rev Immunol 32:283–321.  https://doi.org/10.1146/annurev-immunol-032712-100024CrossRefPubMedPubMedCentralGoogle Scholar
  198. Rothenberg EV, Moore JE, Yui MA (2008) Launching the T-cell-lineage developmental programme. Nat Rev Immunol 8:9–21.  https://doi.org/10.1038/nri2232CrossRefPubMedPubMedCentralGoogle Scholar
  199. Rothenberg EV, Zhang J, Li L (2010) Multilayered specification of the T-cell lineage fate. Immunol Rev 238:150–168.  https://doi.org/10.1111/j.1600-065X.2010.00964.xCrossRefPubMedPubMedCentralGoogle Scholar
  200. Rothenberg EV, Ungerback J, Champhekar A (2016) Forging T-lymphocyte identity: intersecting networks of transcriptional control. Adv Immunol 129:109–174.  https://doi.org/10.1016/bs.ai.2015.09.002CrossRefPubMedPubMedCentralGoogle Scholar
  201. Roy S et al (2018) Id proteins suppress E2A-driven invariant natural killer T cell development prior to TCR selection. Front Immunol 9:42.  https://doi.org/10.3389/fimmu.2018.00042CrossRefPubMedPubMedCentralGoogle Scholar
  202. Sambandam A et al (2005) Notch signaling controls the generation and differentiation of early T lineage progenitors. Nat Immunol 6:663–670.  https://doi.org/10.1038/ni1216CrossRefPubMedPubMedCentralGoogle Scholar
  203. Sawada S, Scarborough JD, Killeen N, Littman DR (1994) A lineage-specific transcriptional silencer regulates CD4 gene expression during T lymphocyte development. Cell 77:917–929PubMedCrossRefPubMedCentralGoogle Scholar
  204. Schmitt TM, Zuniga-Pflucker JC (2002) Induction of T cell development from hematopoietic progenitor cells by delta-like-1 in vitro. Immunity 17:749–756PubMedCrossRefGoogle Scholar
  205. Schmitt TM, Ciofani M, Petrie HT, Zuniga-Pflucker JC (2004) Maintenance of T cell specification and differentiation requires recurrent notch receptor-ligand interactions. J Exp Med 200:469–479.  https://doi.org/10.1084/jem.20040394CrossRefPubMedPubMedCentralGoogle Scholar
  206. Schwarz BA, Bhandoola A (2004) Circulating hematopoietic progenitors with T lineage potential. Nat Immunol 5:953–960.  https://doi.org/10.1038/ni1101CrossRefPubMedPubMedCentralGoogle Scholar
  207. Schwarz BA, Sambandam A, Maillard I, Harman BC, Love PE, Bhandoola A (2007) Selective thymus settling regulated by cytokine and chemokine receptors. J Immunol 178:2008–2017PubMedCrossRefPubMedCentralGoogle Scholar
  208. Scott EW, Simon MC, Anastasi J, Singh H (1994) Requirement of transcription factor PU.1 in the development of multiple hematopoietic lineages. Science 265:1573–1577PubMedCrossRefPubMedCentralGoogle Scholar
  209. Seddiki N et al (2006) Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J Exp Med 203:1693–1700.  https://doi.org/10.1084/jem.20060468CrossRefPubMedPubMedCentralGoogle Scholar
  210. Serwold T, Ehrlich LI, Weissman IL (2009) Reductive isolation from bone marrow and blood implicates common lymphoid progenitors as the major source of thymopoiesis. Blood 113:807–815.  https://doi.org/10.1182/blood-2008-08-173682CrossRefPubMedPubMedCentralGoogle Scholar
  211. Shi J, Fallahi M, Luo JL, Petrie HT (2011) Nonoverlapping functions for Notch1 and Notch3 during murine steady-state thymic lymphopoiesis. Blood 118:2511–2519.  https://doi.org/10.1182/blood-2011-04-346726CrossRefPubMedPubMedCentralGoogle Scholar
  212. Shibata K et al (2011) Notch-Hes1 pathway is required for the development of IL-17-producing gammadelta T cells. Blood 118:586–593.  https://doi.org/10.1182/blood-2011-02-334995CrossRefPubMedPubMedCentralGoogle Scholar
  213. Singer A (2002) New perspectives on a developmental dilemma: the kinetic signaling model and the importance of signal duration for the CD4/CD8 lineage decision. Curr Opin Immunol 14:207–215PubMedCrossRefPubMedCentralGoogle Scholar
  214. Singer A, Adoro S, Park JH (2008) Lineage fate and intense debate: myths, models and mechanisms of CD4- versus CD8-lineage choice. Nat Rev Immunol 8:788–801.  https://doi.org/10.1038/nri2416CrossRefPubMedPubMedCentralGoogle Scholar
  215. Six EM et al (2007) A human postnatal lymphoid progenitor capable of circulating and seeding the thymus. J Exp Med 204:3085–3093.  https://doi.org/10.1084/jem.20071003CrossRefPubMedPubMedCentralGoogle Scholar
  216. Sleasman JW, Harville TO, White GB, George JF, Barrett DJ, Goodenow MM (1994) Arrested rearrangement of TCR V beta genes in thymocytes from children with X-linked severe combined immunodeficiency disease. J Immunol 153:442–448PubMedPubMedCentralGoogle Scholar
  217. Spangrude GJ, Scollay R (1990) Differentiation of hematopoietic stem cells in irradiated mouse thymic lobes. Kinetics and phenotype of progeny. J Immunol 145:3661–3668PubMedPubMedCentralGoogle Scholar
  218. Spits H (2002) Development of alphabeta T cells in the human thymus. Nat Rev Immunol 2:760–772PubMedCrossRefPubMedCentralGoogle Scholar
  219. Spits H, Lanier LL, Phillips JH (1995) Development of human T and natural killer cells. Blood 85:2654–2670PubMedPubMedCentralGoogle Scholar
  220. Spits H et al (1998) Early stages in the development of human T, natural killer and thymic dendritic cells. Immunol Rev 165:75–86PubMedCrossRefPubMedCentralGoogle Scholar
  221. Spits H, Couwenberg F, Bakker AQ, Weijer K, Uittenbogaart CH (2000) Id2 and Id3 inhibit development of CD34(+) stem cells into predendritic cell (pre-DC)2 but not into pre-DC1. Evidence for a lymphoid origin of pre-DC2. J Exp Med 192:1775–1784PubMedPubMedCentralCrossRefGoogle Scholar
  222. Suliman S et al (2011) Notch3 is dispensable for thymocyte beta-selection and Notch1-induced T cell leukemogenesis. PLoS One 6:e24937.  https://doi.org/10.1371/journal.pone.0024937CrossRefPubMedPubMedCentralGoogle Scholar
  223. Sun G et al (2005) The zinc finger protein cKrox directs CD4 lineage differentiation during intrathymic T cell positive selection. Nat Immunol 6:373–381.  https://doi.org/10.1038/ni1183CrossRefPubMedPubMedCentralGoogle Scholar
  224. Sutton CE, Lalor SJ, Sweeney CM, Brereton CF, Lavelle EC, Mills KH (2009) Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity. Immunity 31:331–341.  https://doi.org/10.1016/j.immuni.2009.08.001CrossRefPubMedPubMedCentralGoogle Scholar
  225. Taghon T, Rothenberg EV (2008) Molecular mechanisms that control mouse and human TCR-alphabeta and TCR-gammadelta T cell development. Semin Immunopathol 30:383–398.  https://doi.org/10.1007/s00281-008-0134-3CrossRefPubMedPubMedCentralGoogle Scholar
  226. Taghon T, De Smedt M, Stolz F, Cnockaert M, Plum J, Leclercq G (2001) Enforced expression of GATA-3 severely reduces human thymic cellularity. J Immunol 167:4468–4475PubMedCrossRefPubMedCentralGoogle Scholar
  227. Taghon T, Stolz F, De Smedt M, Cnockaert M, Verhasselt B, Plum J, Leclercq G (2002) HOX-A10 regulates hematopoietic lineage commitment: evidence for a monocyte-specific transcription factor. Blood 99:1197–1204PubMedCrossRefPubMedCentralGoogle Scholar
  228. Taghon TN, David ES, Zuniga-Pflucker JC, Rothenberg EV (2005) Delayed, asynchronous, and reversible T-lineage specification induced by Notch/Delta signaling. Genes Dev 19:965–978.  https://doi.org/10.1101/gad.1298305CrossRefPubMedPubMedCentralGoogle Scholar
  229. Taghon T, Yui MA, Pant R, Diamond RA, Rothenberg EV (2006) Developmental and molecular characterization of emerging beta- and gammadelta-selected pre-T cells in the adult mouse thymus. Immunity 24:53–64.  https://doi.org/10.1016/j.immuni.2005.11.012CrossRefPubMedPubMedCentralGoogle Scholar
  230. Taghon T, Van de Walle I, De Smet G, De Smedt M, Leclercq G, Vandekerckhove B, Plum J (2009) Notch signaling is required for proliferation but not for differentiation at a well-defined beta-selection checkpoint during human T-cell development. Blood 113:3254–3263.  https://doi.org/10.1182/blood-2008-07-168906CrossRefPubMedPubMedCentralGoogle Scholar
  231. Taghon T, Waegemans E, Van de Walle I (2012) Notch signaling during human T cell development. Curr Top Microbiol Immunol 360:75–97PubMedPubMedCentralGoogle Scholar
  232. Takaba H, Takayanagi H (2017) The mechanisms of T cell selection in the thymus. Trends Immunol 38:805–816.  https://doi.org/10.1016/j.it.2017.07.010CrossRefPubMedPubMedCentralGoogle Scholar
  233. Takaba H et al (2015) Fezf2 orchestrates a thymic program of self-antigen expression for immune tolerance. Cell 163:975–987.  https://doi.org/10.1016/j.cell.2015.10.013CrossRefPubMedPubMedCentralGoogle Scholar
  234. Tan JB, Visan I, Yuan JS, Guidos CJ (2005) Requirement for Notch1 signals at sequential early stages of intrathymic T cell development. Nat Immunol 6:671–679.  https://doi.org/10.1038/ni1217CrossRefPubMedPubMedCentralGoogle Scholar
  235. Tanigaki K et al (2004) Regulation of alphabeta/gammadelta T cell lineage commitment and peripheral T cell responses by Notch/RBP-J signaling. Immunity 20:611–622PubMedCrossRefPubMedCentralGoogle Scholar
  236. Taniuchi I et al (2002a) Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development. Cell 111:621–633PubMedCrossRefGoogle Scholar
  237. Taniuchi I, Sunshine MJ, Festenstein R, Littman DR (2002b) Evidence for distinct CD4 silencer functions at different stages of thymocyte differentiation. Mol Cell 10:1083–1096PubMedCrossRefGoogle Scholar
  238. Terstappen LW, Huang S, Picker LJ (1992) Flow cytometric assessment of human T-cell differentiation in thymus and bone marrow. Blood 79:666–677PubMedPubMedCentralGoogle Scholar
  239. Thompson PK, Zuniga-Pflucker JC (2011) On becoming a T cell, a convergence of factors kick it up a Notch along the way. Semin Immunol 23:350–359.  https://doi.org/10.1016/j.smim.2011.08.007CrossRefPubMedPubMedCentralGoogle Scholar
  240. Treiner E, Lantz O (2006) CD1d- and MR1-restricted invariant T cells: of mice and men. Curr Opin Immunol 18:519–526.  https://doi.org/10.1016/j.coi.2006.07.001CrossRefPubMedGoogle Scholar
  241. Treiner E et al (2003) Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1. Nature 422:164–169.  https://doi.org/10.1038/nature01433CrossRefPubMedPubMedCentralGoogle Scholar
  242. Treiner E, Duban L, Moura IC, Hansen T, Gilfillan S, Lantz O (2005) Mucosal-associated invariant T (MAIT) cells: an evolutionarily conserved T cell subset. Microbes Infect 7:552–559.  https://doi.org/10.1016/j.micinf.2004.12.013CrossRefPubMedPubMedCentralGoogle Scholar
  243. Tuovinen H, Kekalainen E, Rossi LH, Puntila J, Arstila TP (2008a) Cutting edge: human CD4-CD8- thymocytes express FOXP3 in the absence of a TCR. J Immunol 180:3651–3654PubMedCrossRefPubMedCentralGoogle Scholar
  244. Tuovinen H, Pekkarinen PT, Rossi LH, Mattila I, Arstila TP (2008b) The FOXP3+ subset of human CD4+CD8+ thymocytes is immature and subject to intrathymic selection. Immunol Cell Biol 86:523–529.  https://doi.org/10.1038/icb.2008.36CrossRefPubMedPubMedCentralGoogle Scholar
  245. Turchinovich G, Hayday AC (2011) Skint-1 identifies a common molecular mechanism for the development of interferon-gamma-secreting versus interleukin-17-secreting gammadelta T cells. Immunity 35:59–68.  https://doi.org/10.1016/j.immuni.2011.04.018CrossRefPubMedPubMedCentralGoogle Scholar
  246. Turchinovich G, Pennington DJ (2011) T cell receptor signalling in gammadelta cell development: strength isn’t everything. Trends Immunol 32:567–573.  https://doi.org/10.1016/j.it.2011.09.005CrossRefPubMedPubMedCentralGoogle Scholar
  247. Uehara S, Grinberg A, Farber JM, Love PE (2002) A role for CCR9 in T lymphocyte development and migration. J Immunol 168:2811–2819PubMedCrossRefPubMedCentralGoogle Scholar
  248. Ueno T et al (2002) Role for CCR7 ligands in the emigration of newly generated T lymphocytes from the neonatal thymus. Immunity 16:205–218PubMedCrossRefPubMedCentralGoogle Scholar
  249. Van Coppernolle S et al (2012) Notch induces human T-cell receptor gammadelta+ thymocytes to differentiate along a parallel, highly proliferative and bipotent CD4 CD8 double-positive pathway. Leukemia 26:127–138.  https://doi.org/10.1038/leu.2011.324CrossRefPubMedPubMedCentralGoogle Scholar
  250. Van de Walle I, De Smet G, De Smedt M, Vandekerckhove B, Leclercq G, Plum J, Taghon T (2009) An early decrease in Notch activation is required for human TCR-alphabeta lineage differentiation at the expense of TCR-gammadelta T cells. Blood 113:2988–2998.  https://doi.org/10.1182/blood-2008-06-164871CrossRefPubMedPubMedCentralGoogle Scholar
  251. Van de Walle I et al (2011) Jagged2 acts as a Delta-like Notch ligand during early hematopoietic cell fate decisions. Blood 117:4449–4459.  https://doi.org/10.1182/blood-2010-06-290049CrossRefPubMedPubMedCentralGoogle Scholar
  252. Van de Walle I et al (2013) Specific Notch receptor-ligand interactions control human TCR-alphabeta/gammadelta development by inducing differential Notch signal strength. J Exp Med 210:683–697.  https://doi.org/10.1084/jem.20121798CrossRefPubMedPubMedCentralGoogle Scholar
  253. Van de Walle I et al (2016) GATA3 induces human T-cell commitment by restraining Notch activity and repressing NK-cell fate. Nat Commun 7:11171.  https://doi.org/10.1038/ncomms11171CrossRefPubMedPubMedCentralGoogle Scholar
  254. Vantourout P, Hayday A (2013) Six-of-the-best: unique contributions of gammadelta T cells to immunology. Nat Rev Immunol 13:88–100.  https://doi.org/10.1038/nri3384CrossRefPubMedPubMedCentralGoogle Scholar
  255. Verschuren MC, Wolvers-Tettero IL, Breit TM, Noordzij J, van Wering ER, van Dongen JJ (1997) Preferential rearrangements of the T cell receptor-delta-deleting elements in human T cells. J Immunol 158:1208–1216PubMedPubMedCentralGoogle Scholar
  256. Verykokakis M, Krishnamoorthy V, Iavarone A, Lasorella A, Sigvardsson M, Kee BL (2013) Essential functions for ID proteins at multiple checkpoints in invariant NKT cell development. J Immunol 191:5973–5983.  https://doi.org/10.4049/jimmunol.1301521CrossRefPubMedGoogle Scholar
  257. Wallis VJ, Leuchars E, Chwalinski S, Davies AJ (1975) On the sparse seeding of bone marrow and thymus in radiation chimaeras. Transplantation 19:2–11PubMedCrossRefPubMedCentralGoogle Scholar
  258. Wang J et al (1998) Atomic structure of an alphabeta T cell receptor (TCR) heterodimer in complex with an anti-TCR fab fragment derived from a mitogenic antibody. EMBO J 17:10–26.  https://doi.org/10.1093/emboj/17.1.10CrossRefPubMedPubMedCentralGoogle Scholar
  259. Wang D et al (2006) The basic helix-loop-helix transcription factor HEBAlt is expressed in pro-T cells and enhances the generation of T cell precursors. J Immunol 177:109–119PubMedCrossRefGoogle Scholar
  260. Wang L et al (2008) Distinct functions for the transcription factors GATA-3 and ThPOK during intrathymic differentiation of CD4(+) T cells. Nat Immunol 9:1122–1130.  https://doi.org/10.1038/ni.1647CrossRefPubMedPubMedCentralGoogle Scholar
  261. Washburn T, Schweighoffer E, Gridley T, Chang D, Fowlkes BJ, Cado D, Robey E (1997) Notch activity influences the alphabeta versus gammadelta T cell lineage decision. Cell 88:833–843PubMedCrossRefGoogle Scholar
  262. Watanabe N, Hanabuchi S, Soumelis V, Yuan W, Ho S, de Waal Malefyt R, Liu YJ (2004) Human thymic stromal lymphopoietin promotes dendritic cell-mediated CD4+ T cell homeostatic expansion. Nat Immunol 5:426–434.  https://doi.org/10.1038/ni1048CrossRefPubMedGoogle Scholar
  263. Watanabe N, Wang YH, Lee HK, Ito T, Wang YH, Cao W, Liu YJ (2005) Hassall’s corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature 436:1181–1185.  https://doi.org/10.1038/nature03886CrossRefPubMedPubMedCentralGoogle Scholar
  264. Weber BN, Chi AW, Chavez A, Yashiro-Ohtani Y, Yang Q, Shestova O, Bhandoola A (2011) A critical role for TCF-1 in T-lineage specification and differentiation. Nature 476:63–68.  https://doi.org/10.1038/nature10279CrossRefPubMedPubMedCentralGoogle Scholar
  265. Weerkamp F, Luis TC, Naber BA, Koster EE, Jeannotte L, van Dongen JJ, Staal FJ (2006) Identification of Notch target genes in uncommitted T-cell progenitors: no direct induction of a T-cell specific gene program. Leukemia 20:1967–1977.  https://doi.org/10.1038/sj.leu.2404396CrossRefPubMedGoogle Scholar
  266. Welner RS et al (2013) C/EBPalpha is required for development of dendritic cell progenitors. Blood 121:4073–4081.  https://doi.org/10.1182/blood-2012-10-463448CrossRefPubMedPubMedCentralGoogle Scholar
  267. Weng AP et al (2006) c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia/lymphoma. Genes Dev 20:2096–2109.  https://doi.org/10.1101/gad.1450406CrossRefPubMedPubMedCentralGoogle Scholar
  268. Wildin RS et al (2001) X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet 27:18–20.  https://doi.org/10.1038/83707CrossRefPubMedGoogle Scholar
  269. Wildt KF, Sun G, Grueter B, Fischer M, Zamisch M, Ehlers M, Bosselut R (2007) The transcription factor Zbtb7b promotes CD4 expression by antagonizing Runx-mediated activation of the CD4 silencer. J Immunol 179:4405–4414PubMedCrossRefGoogle Scholar
  270. Wilson A, MacDonald HR, Radtke F (2001) Notch 1-deficient common lymphoid precursors adopt a B cell fate in the thymus. J Exp Med 194:1003–1012PubMedPubMedCentralCrossRefGoogle Scholar
  271. Witt CM, Hurez V, Swindle CS, Hamada Y, Klug CA (2003) Activated Notch2 potentiates CD8 lineage maturation and promotes the selective development of B1 B cells. Mol Cell Biol 23:8637–8650PubMedCrossRefGoogle Scholar
  272. Wojciechowski J, Lai A, Kondo M, Zhuang Y (2007) E2A and HEB are required to block thymocyte proliferation prior to pre-TCR expression. J Immunol 178:5717–5726PubMedPubMedCentralCrossRefGoogle Scholar
  273. Wolfer A et al (2001) Inactivation of Notch 1 in immature thymocytes does not perturb CD4 or CD8T cell development. Nat Immunol 2:235–241.  https://doi.org/10.1038/85294CrossRefPubMedGoogle Scholar
  274. Wong GW, Zuniga-Pflucker JC (2010) gammadelta and alphabeta T cell lineage choice: resolution by a stronger sense of being. Semin Immunol 22:228–236.  https://doi.org/10.1016/j.smim.2010.04.005CrossRefPubMedGoogle Scholar
  275. Wong GW, Knowles GC, Mak TW, Ferrando AA, Zuniga-Pflucker JC (2012) HES1 opposes a PTEN-dependent check on survival, differentiation, and proliferation of TCRbeta-selected mouse thymocytes. Blood 120:1439–1448.  https://doi.org/10.1182/blood-2011-12-395319CrossRefPubMedPubMedCentralGoogle Scholar
  276. Xiong Y, Bosselut R (2012) CD4-CD8 differentiation in the thymus: connecting circuits and building memories. Curr Opin Immunol 24:139–145.  https://doi.org/10.1016/j.coi.2012.02.002CrossRefPubMedPubMedCentralGoogle Scholar
  277. Xu W, Carr T, Ramirez K, McGregor S, Sigvardsson M, Kee BL (2013) E2A transcription factors limit expression of Gata3 to facilitate T lymphocyte lineage commitment. Blood 121:1534–1542.  https://doi.org/10.1182/blood-2012-08-449447CrossRefPubMedPubMedCentralGoogle Scholar
  278. Yamasaki S et al (2006) Mechanistic basis of pre-T cell receptor-mediated autonomous signaling critical for thymocyte development. Nat Immunol 7:67–75.  https://doi.org/10.1038/ni1290CrossRefPubMedGoogle Scholar
  279. Yashiro-Ohtani Y et al (2009) Pre-TCR signaling inactivates Notch1 transcription by antagonizing E2A. Genes Dev 23:1665–1676.  https://doi.org/10.1101/gad.1793709CrossRefPubMedPubMedCentralGoogle Scholar
  280. Yokota Y, Mansouri A, Mori S, Sugawara S, Adachi S, Nishikawa S, Gruss P (1999) Development of peripheral lymphoid organs and natural killer cells depends on the helix-loop-helix inhibitor Id2. Nature 397:702–706.  https://doi.org/10.1038/17812CrossRefPubMedGoogle Scholar
  281. Yu VW et al (2015) Specific bone cells produce DLL4 to generate thymus-seeding progenitors from bone marrow. J Exp Med 212:759–774.  https://doi.org/10.1084/jem.20141843CrossRefPubMedPubMedCentralGoogle Scholar
  282. Yui MA, Rothenberg EV (2014) Developmental gene networks: a triathlon on the course to T cell identity. Nat Rev Immunol 14:529–545.  https://doi.org/10.1038/nri3702CrossRefPubMedPubMedCentralGoogle Scholar
  283. Yui MA, Feng N, Rothenberg EV (2010) Fine-scale staging of T cell lineage commitment in adult mouse thymus. J Immunol 185:284–293.  https://doi.org/10.4049/jimmunol.1000679CrossRefPubMedPubMedCentralGoogle Scholar
  284. Yun TJ, Bevan MJ (2003) Notch-regulated ankyrin-repeat protein inhibits Notch1 signaling: multiple Notch1 signaling pathways involved in T cell development. J Immunol 170:5834–5841PubMedCrossRefPubMedCentralGoogle Scholar
  285. Zarin P, Wong GW, Mohtashami M, Wiest DL, Zuniga-Pflucker JC (2014) Enforcement of gammadelta-lineage commitment by the pre-T-cell receptor in precursors with weak gammadelta-TCR signals. Proc Natl Acad Sci U S A 111:5658–5663.  https://doi.org/10.1073/pnas.1312872111CrossRefPubMedPubMedCentralGoogle Scholar
  286. Zarin P, Chen EL, In TS, Anderson MK, Zuniga-Pflucker JC (2015) Gamma delta T-cell differentiation and effector function programming, TCR signal strength, when and how much? Cell Immunol 296:70–75.  https://doi.org/10.1016/j.cellimm.2015.03.007CrossRefPubMedGoogle Scholar
  287. Zarin P et al (2018) Integration of T-cell receptor, Notch and cytokine signals programs mouse gammadelta T-cell effector differentiation. Immunol Cell Biol 96:994.  https://doi.org/10.1111/imcb.12164CrossRefPubMedPubMedCentralGoogle Scholar
  288. Zhang DE, Zhang P, Wang ND, Hetherington CJ, Darlington GJ, Tenen DG (1997) Absence of granulocyte colony-stimulating factor signaling and neutrophil development in CCAAT enhancer binding protein alpha-deficient mice. Proc Natl Acad Sci U S A 94:569–574PubMedPubMedCentralCrossRefGoogle Scholar
  289. Zhang JA, Mortazavi A, Williams BA, Wold BJ, Rothenberg EV (2012) Dynamic transformations of genome-wide epigenetic marking and transcriptional control establish T cell identity. Cell 149:467–482.  https://doi.org/10.1016/j.cell.2012.01.056CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Kogulan Yoganathan
    • 1
  • Edward L. Y. Chen
    • 1
  • Jastaranpreet Singh
    • 1
  • Juan Carlos Zúñiga-Pflücker
    • 1
    Email author
  1. 1.Department of Immunology, Sunnybrook Research InstituteUniversity of TorontoTorontoCanada

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