Development and Function of Cortical Thymic Epithelial Cells

  • Kensuke Takada
  • Izumi Ohigashi
  • Michiyuki Kasai
  • Hiroshi Nakase
  • Yousuke TakahamaEmail author
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 373)


The thymic cortex provides a microenvironment that supports the generation and T cell antigen receptor (TCR)-mediated selection of CD4+CD8+TCRαβ+ thymocytes. Cortical thymic epithelial cells (cTECs) are the essential component that forms the architecture of the thymic cortex and induces the generation as well as the selection of newly generated T cells. Here we summarize current knowledge on the development, function, and heterogeneity of cTECs, focusing on the expression and function of β5t, a cTEC-specific subunit of the thymoproteasome.


Pharyngeal Pouch Fetal Thymus Thymic Cortex Single Positive Thymocyte Thymic Nurse Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by Grants-in-Aid for Scientific Research from MEXT and JSPS (grant numbers 23249025 and 24111004).


  1. Adriani M, Martinez-Mir A, Fusco F, Busiello R, Frank J, Telese S, Matrecano E, Ursini MV, Christiano AM, Pignata C (2004) Ancestral founder mutation of the nude (FOXN1) gene in congenital severe combined immunodeficiency associated with alopecia in southern Italy population. Ann Hum Genet 68:265–268PubMedGoogle Scholar
  2. Aguilar LK, Agilar-Cordova E, Cartwright J Jr, Belmont JW (1994) Thymic nurse cells are sites of thymocyte apoptosis. J Immunol 152:2645–2651PubMedGoogle Scholar
  3. Akiyama T, Maeda S, Yamane S, Ogino K, Kasai M, Kajiura F, Matsumoto M, Inoue J (2005) Dependence of self-tolerance on TRAF6-directed development of thymic stroma. Science 308:248–251PubMedGoogle Scholar
  4. Akiyama T, Shimo Y, Yanai H, Qin J, Ohshima D, Maruyama Y, Asaumi Y, Kitazawa J, Takayanagi H, Penninger JM, Matsumoto M, Nitta T, Takahama Y, Inoue J (2008) The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance. Immunity 29:423–437PubMedGoogle Scholar
  5. Alves NL, Huntington ND, Rodewald HR, Di Santo JP (2009) Thymic epithelial cells: the multi-tasking framework of the T cell “cradle”. Trends Immunol 30:468–474PubMedGoogle Scholar
  6. Bell JJ, Bhandoola A (2008) The earliest thymic progenitors for T cells possess myeloid lineage potential. Nature 452:764–767PubMedGoogle Scholar
  7. Bennett AR, Farley A, Blair NF, Gordon J, Sharp L, Blackburn CC (2002) Identification and characterization of thymic epithelial progenitor cells. Immunity 16:803–814PubMedGoogle Scholar
  8. Blackburn CC, Augustine CL, Li R, Harvey RP, Malin MA, Boyd RL, Miller JF, Morahan G (1996) The nu gene acts cell-autonomously and is required for differentiation of thymic epithelial progenitors. Proc Natl Acad Sci USA 93:5742–5746PubMedGoogle Scholar
  9. Bleul CC, Carbeaux T, Reuter A, Fisch P, Monting JS, Boehm T (2006) Formation of a functional thymus initiated by a postnatal epithelial progenitor cell. Nature 441:992–996PubMedGoogle Scholar
  10. Boehm T, Scheu S, Pfeffer K, Bleul CC (2003) Thymic medullary epithelial cell differentiation, thymocyte emigration, and the control of autoimmunity require lympho-epithelial cross talk via LTβR. J Exp Med 198:757–769PubMedGoogle Scholar
  11. Boehm T (2009) The adaptive phenotype of cortical thymic epithelial cells. Eur J Immunol 39:944–947PubMedGoogle Scholar
  12. Bowlus CL, Ahn J, Chu T, Gruen JR (1999) Cloning of a novel MHC-encoded serine peptidase highly expressed by cortical epithelial cells of the thymus. Cell Immunol 196:80–86PubMedGoogle Scholar
  13. Boyd RL, Tucek CL, Godfrey DI, Izon DJ, Wilson TJ, Davidson NJ, Bean AG, Ladyman HM, Ritter MA, Hugo P (1993) The thymic microenvironment. Immunol Today 14:445–459PubMedGoogle Scholar
  14. Burkly L, Hession C, Ogata L, Reilly C, Marconi LA, Olson D, Tizard R, Cate R, Lo D (1995) Expression of relB is required for the development of thymic medulla and dendritic cells. Nature 373:531–536PubMedGoogle Scholar
  15. Calderón L, Boehm T (2011) Three chemokine receptors cooperatively regulate homing of hematopoietic progenitors to the embryonic mouse thymus. Proc Natl Acad Sci USA 108:7517–7522PubMedGoogle Scholar
  16. Carrier A, Nguyen C, Victorero G, Granjeaud S, Rocha D, Bernard K, Miazek A, Ferrier P, Malissen M, Naquet P, Malissen B, Jordan BR (1999) Differential gene expression in CD3epsilon- and RAG1-deficient thymuses: definition of a set of genes potentially involved in thymocyte maturation. Immunogenetics 50:255–270PubMedGoogle Scholar
  17. Cheunsuk S, Lian ZX, Yang GX, Gershwin ME, Gruen JR, Bowlus CL (2005) Prss16 is not required for T-cell development. Mol Cell Biol 25:789–796PubMedGoogle Scholar
  18. Ciofani M, Zúñiga-Pflücker JC (2005) Notch promotes survival of pre-T cells at the beta-selection checkpoint by regulating cellular metabolism. Nat Immunol 6:881–888PubMedGoogle Scholar
  19. de Waal Malefijt R, Leene W, Roholl PJ, Wormmeester J, Hoeben KA (1986) T cell differentiation within thymic nurse cells. Lab Invest 55:25–34PubMedGoogle Scholar
  20. Douek DC, McFarland RD, Keiser PH, Gage EA, Massey JM, Haynes BF, Polis MA, Haase AT, Feinberg MB, Sullivan JL, Jamieson BD, Zack JA, Picker LJ, Koup RA (1998) Changes in thymic function with age and during the treatment of HIV infection. Nature 396:690–695PubMedGoogle Scholar
  21. Fiorini E, Ferrero I, Merck E, Favre S, Pierres M, Luther SA, MacDonald HR (2008) Thymic crosstalk regulates delta-like 4 expression on cortical epithelial cells. J Immunol 181:8199–8203PubMedGoogle Scholar
  22. Flaño E, Alvarez F, López-Fierro P, Razquin BE, Villena AJ, Zapata AG (1996) In vitro and in situ characterization of fish thymic nurse cells. Dev Immunol 5:17–24PubMedGoogle Scholar
  23. Florea BI, Verdoes M, Li N, van der Linden WA, Geurink PP, van den Elst H, Hofmann T, de Ru A, van Veelen PA, Tanaka K, Sasaki K, Murata S, den Dulk H, Brouwer J, Ossendorp FA, Kisselev AF, Overkleeft HS (2010) Activity-based profiling reveals reactivity of the murine thymoproteasome-specific subunit β5t. Chem Biol 17:795–801PubMedGoogle Scholar
  24. Gill J, Malin M, Holländer GA, Boyd R (2002) Generation of a complete thymic microenvironment by MTS24+ thymic epithelial cells. Nat Immunol 3:635–642PubMedGoogle Scholar
  25. Gommeaux J, Grégoire C, Nguessan P, Richelme M, Malissen M, Guerder S, Malissen B, Carrier A (2009) Thymus-specific serine protease regulates positive selection of a subset of CD4+ thymocytes. Eur J Immunol 39:956–964PubMedGoogle Scholar
  26. Gordon J, Bennett AR, Blackburn CC, Manley NR (2001) Gcm2 and Foxn1 mark early parathyroid- and thymus-specific domains in the developing third pharyngeal pouch. Mech Dev 103:141–143PubMedGoogle Scholar
  27. Gordon J, Wilson VA, Blair NF, Sheridan J, Farley A, Wilson L, Manley NR, Blackburn CC (2004) Functional evidence for a single endodermal origin for the thymic epithelium. Nat Immunol 5:546–553PubMedGoogle Scholar
  28. Gray DH, Seach N, Ueno T, Milton MK, Liston A, Lew AM, Goodnow CC, Boyd RL (2006) Developmental kinetics, turnover, and stimulatory capacity of thymic epithelial cells. Blood 108:3777–3785PubMedGoogle Scholar
  29. Griffith AV, Fallahi M, Nakase H, Gosink M, Young B, Petrie HT (2009) Spatial mapping of thymic stromal microenvironments reveals unique features influencing T lymphoid differentiation. Immunity 31:999–1009PubMedGoogle Scholar
  30. Guyden JC, Pezzano M (2003) Thymic nurse cells: a microenvironment for thymocyte development and selection. Int Rev Cytol 223:1–37PubMedGoogle Scholar
  31. Hamazaki Y, Fujita H, Kobayashi T, Choi Y, Scott HS, Matsumoto M, Minato N (2007) Medullary thymic epithelial cells expressing Aire represent a unique lineage derived from cells expressing claudin. Nat Immunol 8:304–311PubMedGoogle Scholar
  32. Hara T, Shitara S, Imai K, Miyachi H, Kitano S, Yao H, Tani-ichi S, Ikuta K (2012) Identification of IL-7-producing cells in primary and secondary lymphoid organs using IL-7-GFP knock-in mice. J Immunol 189:1577–1584PubMedGoogle Scholar
  33. Hetzer-Egger C, Schorpp M, Haas-Assenbaum A, Balling R, Peters H, Boehm T (2002) Thymopoiesis requires Pax9 function in thymic epithelial cells. Eur J Immunol 32:1175–1181PubMedGoogle Scholar
  34. Hikosaka Y, Nitta T, Ohigashi I, Yano K, Ishimaru N, Hayashi Y, Matsumoto M, Matsuo K, Penninger JM, Takayanagi H, Yokota Y, Yamada H, Yoshikai Y, Inoue J, Akiyama T, Takahama Y (2008) The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator. Immunity 29:438–450PubMedGoogle Scholar
  35. Holländer GA, Wang B, Nichogiannopoulou A, Platenburg PP, van Ewijk W, Burakoff SJ, Gutierrez-Ramos JC, Terhorst C (1995) Developmental control point in induction of thymic cortex regulated by a subpopulation of prothymocytes. Nature 373:350–353PubMedGoogle Scholar
  36. Honey K, Nakagawa T, Peters C, Rudensky A (2002) Cathepsin L regulates CD4+ T cell selection independently of its effect on invariant chain: a role in the generation of positively selecting peptide ligands. J Exp Med 195:1349–1358PubMedGoogle Scholar
  37. Hozumi K, Negishi N, Suzuki D, Abe N, Sotomaru Y, Tamaoki N, Mailhos C, Ish-Horowicz D, Habu S, Owen MJ (2004) Delta-like 1 is necessary for the generation of marginal zone B cells but not T cells in vivo. Nat Immunol 5:638–644PubMedGoogle Scholar
  38. Hozumi K, Mailhos C, Negishi N, Hirano K, Yahata T, Ando K, Zuklys S, Holländer GA, Shima DT, Habu S (2008) Delta-like 4 is indispensable in thymic environment specific for T cell development. J Exp Med 205:2507–2513PubMedGoogle Scholar
  39. Hu B, Lefort K, Qiu W, Nguyen BC, Rajaram RD, Castillo E, He F, Chen Y, Angel P, Brisken C, Dotto GP (2010) Control of hair follicle cell fate by underlying mesenchyme through a CSL-Wnt5a-FoxN1 regulatory axis. Genes Dev 24:1519–1532PubMedGoogle Scholar
  40. Jerome LA, Papaioannou VE (2001) DiGeorge syndrome phenotype in mice mutant for the T-box gene. Tbx. Nat Genet 27:286–291Google Scholar
  41. Klug DB, Carter C, Crouch E, Roop D, Conti CJ, Richie ER (1998) Interdependence of cortical thymic epithelial cell differentiation and T-lineage commitment. Proc Natl Acad Sci USA 95:11822–11827PubMedGoogle Scholar
  42. Klug DB, Carter C, Gimenez-Conti IB, Richie ER (2002) Thymocyte-independent and thymocyte-dependent phases of epithelial patterning in the fetal thymus. J Immunol 169:2842–2845PubMedGoogle Scholar
  43. Koch U, Fiorini E, Benedito R, Besseyrias V, Schuster-Gossler K, Pierres M, Manley NR, Duarte A, Macdonald HR, Radtke F (2008) Delta-like 4 is the essential, nonredundant ligand for Notch1 during thymic T cell lineage commitment. J Exp Med 205:2515–2523PubMedGoogle Scholar
  44. Kondo M, Akashi K, Domen J, Sugamura K, Weissman IL (1997) Bcl-2 rescues T lymphopoiesis, but not B or NK cell development, in common gamma chain-deficient mice. Immunity 7:155–162PubMedGoogle Scholar
  45. Kyewski BA, Kaplan HS (1982) Lymphoepithelial interactions in the mouse thymus: phenotypic and kinetic studies on thymic nurse cells. J Immunol 128:2287–2294PubMedGoogle Scholar
  46. Laufer TM, DeKoning J, Markowitz JS, Lo D, Glimcher LH (1996) Unopposed positive selection and autoreactivity in mice expressing class II MHC only on thymic cortex. Nature 383:81–85PubMedGoogle Scholar
  47. Lindsay EA, Vitelli F, Su H, Morishima M, Huynh T, Pramparo T, Jurecic V, Ogunrinu G, Sutherland HF, Scambler PJ, Bradley A, Baldini A (2001) Tbx1 haploinsufficiency in the DiGeorge syndrome region causes aortic arch defects in mice. Nature 410:97–101PubMedGoogle Scholar
  48. Liu C, Saito F, Liu Z, Lei Y, Uehara S, Love P, Lipp M, Kondo S, Manley N, Takahama Y (2006) Coordination between CCR7- and CCR9-mediated chemokine signals in prevascular fetal thymus colonization. Blood 108:2531–2539PubMedGoogle Scholar
  49. Maillard I, Tu L, Sambandam A, Yashiro-Ohtani Y, Millholland J, Keeshan K, Shestova O, Xu L, Bhandoola A, Pear WS (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 203:2239–2245PubMedGoogle Scholar
  50. Manley NR, Capecchi MR (1995) The role of Hoxa-3 in mouse thymus and thyroid development. Development 121:1989–2003PubMedGoogle Scholar
  51. Maraskovsky E, O’Reilly LA, Teepe M, Corcoran LM, Peschon JJ, Strasser A (1997) Bcl-2 can rescue T lymphocyte development in interleukin-7 receptor-deficient mice but not in mutant rag-1−/− mice. Cell 89:1011–1019PubMedGoogle Scholar
  52. Mat Ripen A, Nitta T, Murata S, Tanaka K, Takahama Y (2011) Ontogeny of thymic cortical epithelial cells expressing the thymoproteasome subunit β5t. Eur J Immunol 41:1278–1287Google Scholar
  53. Mazzucchelli RI, Warming S, Lawrence SM, Ishii M, Abshari M, Washington AV, Feigenbaum L, Warner AC, Sims DJ, Li WQ, Hixon JA, Gray DH, Rich BE, Morrow M, Anver MR, Cherry J, Naf D, Sternberg LR, McVicar DW, Farr AG, Germain RN, Rogers K, Jenkins NA, Copeland NG, Durum SK (2009) Visualization and identification of IL-7 producing cells in reporter mice. PLoS One 4:7637Google Scholar
  54. Merscher S, Funke B, Epstein JA, Heyer J, Puech A, Lu MM, Xavier RJ, Demay MB, Russell RG, Factor S, Tokooya K, Jore BS, Lopez M, Pandita RK, Lia M, Carrion D, Xu H, Schorle H, Kobler JB, Scambler P, Wynshaw-Boris A, Skoultchi AI, Morrow BE, Kucherlapati R (2001) TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome. Cell 104:619–629PubMedGoogle Scholar
  55. Murata S, Sasaki K, Kishimoto T, Niwa S, Hayashi H, Takahama Y, Tanaka K (2007) Regulation of CD8+ T cell development by thymus-specific proteasomes. Science 316:1349–1353PubMedGoogle Scholar
  56. Murata S, Yashiroda H, Tanaka K (2009) Molecular mechanisms of proteasome assembly. Nat Rev Mol Cell Biol 10:104–115PubMedGoogle Scholar
  57. Nakagawa T, Roth W, Wong P, Nelson A, Farr A, Deussing J, Villadangos JA, Ploegh H, Peters C, Rudensky AY (1998) Cathepsin L: critical role in Ii degradation and CD4 T cell selection in the thymus. Science 280:450–453PubMedGoogle Scholar
  58. Nakagawa Y, Ohigashi I, Nitta T, Sakata M, Tanaka K, Murata S, Kanagawa O, Takahama Y (2012) Thymic nurse cells provide microenvironment for secondary TCRα rearrangement in cortical thymocytes. Proc Natl Acad Sci USA 109:20572–20577 Google Scholar
  59. Nedjic J, Aichinger M, Emmerich J, Mizushima N, Klein L (2008) Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance. Nature 455:396–400PubMedGoogle Scholar
  60. Neefjes J, Jongsma ML, Paul P, Bakke O (2011) Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat Rev Immunol 11:823–836PubMedGoogle Scholar
  61. Nehls M, Pfeifer D, Schorpp M, Hedrich H, Boehm T (1994) New member of the winged-helix protein family disrupted in mouse and rat nude mutations. Nature 372:103–107PubMedGoogle Scholar
  62. Nehls M, Kyewski B, Messerle M, Waldschutz R, Schüddekopf K, Smith AJH, Boehm T (1996) Two genetically separable steps in the differentiation of thymic epithelium. Science 272:886–889PubMedGoogle Scholar
  63. Nishikawa Y, Hirota F, Yano M, Kitajima H, Miyazaki J, Kawamoto H, Mouri Y, Matsumoto M (2010) Biphasic Aire expression in early embryos and in medullary thymic epithelial cells before end-stage terminal differentiation. J Exp Med 207:963–971PubMedGoogle Scholar
  64. Nitta T, Murata S, Sasaki K, Fujii H, Ripen AM, Ishimaru N, Koyasu S, Tanaka K, Takahama Y (2010) Thymoproteasome shapes immunocompetent repertoire of CD8+ T cells. Immunity 32:29–40PubMedGoogle Scholar
  65. Park JH, Adoro S, Guinter T, Erman B, Alag AS, Catalfamo M, Kimura MY, Cui Y, Lucas PJ, Gress RE, Kubo M, Hennighausen L, Feigenbaum L, Singer A (2010) Signaling by intrathymic cytokines, not T cell antigen receptors, specifies CD8 lineage choice and promotes the differentiation of cytotoxic-lineage T cells. Nat Immunol 11:257–264PubMedGoogle Scholar
  66. Pellegrini M, Bouillet P, Robati M, Belz GT, Davey GM, Strasser A (2004) Loss of Bim increases T cell production and function in interleukin 7 receptor-deficient mice. J Exp Med 200:1189–1195PubMedGoogle Scholar
  67. Peschon JJ, Morrissey PJ, Grabstein KH, Ramsdell FJ, Maraskovsky E, Gliniak BC, Park LS, Ziegler SF, Williams DE, Ware CB, Meyer JD, Davison BL (1994) Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J Exp Med 180:1955–1960PubMedGoogle Scholar
  68. Pezzano M, Samms M, Martinez M, Guyden J (2001) Questionable thymic nurse cell. Microbiol Mol Biol Rev 65:390–403PubMedGoogle Scholar
  69. 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 10:547–558PubMedGoogle Scholar
  70. Radtke F, Wilson A, Mancini SJ, MacDonald HR (2004) Notch regulation of lymphocyte development and function. Nat Immunol 5:247–253PubMedGoogle Scholar
  71. Rieker T, Penninger J, Romani N, Wick G (1995) Chicken thymic nurse cells: an overview. Dev Comp Immunol 19:281–289PubMedGoogle Scholar
  72. Ritter MA, Sauvage CA, Cotmore SF (1981) The human thymus microenvironment: in vivo identification of thymic nurse cells and other antigenically-distinct subpopulations of epithelial cells. Immunology 44:439–446PubMedGoogle Scholar
  73. Rock KL, Goldberg AL (1999) Degradation of cell proteins and the generation of MHC class I-presented peptides. Annu Rev Immunol 17:739–779PubMedGoogle Scholar
  74. Rode I, Boehm T (2012) Regenerative capacity of adult cortical thymic epithelial cells. Proc Natl Acad Sci USA 109:3463–3468PubMedGoogle Scholar
  75. Rossi SW, Jenkinson WE, Anderson G, Jenkinson EJ (2006) Clonal analysis reveals a common progenitor for thymic cortical and medullary epithelium. Nature 441:988–991PubMedGoogle Scholar
  76. Rossi SW, Kim MY, Leibbrandt A, Parnell SM, Jenkinson WE, Glanville SH, McConnell FM, Scott HS, Penninger JM, Jenkinson EJ, Lane PJ, Anderson G (2007) RANK signals from CD4+3 inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla. J Exp Med 204:1267–1272PubMedGoogle Scholar
  77. Rudd BD, Venturi V, Li G, Samadder P, Ertelt JM, Way SS, Davenport MP, Nikolich-Žugich J (2011) Nonrandom attrition of the naive CD8+ T-cell pool with aging governed by T-cell receptor: pMHC interactions. Proc Natl Acad Sci USA 108:13694–13699PubMedGoogle Scholar
  78. Schaller CE, Wang CL, Beck-Engeser G, Goss L, Scott HS, Anderson MS, Wabl M (2008) Expression of Aire and the early wave of apoptosis in spermatogenesis. J Immunol 180:1338–1343PubMedGoogle Scholar
  79. Schmitt TM, Zúñiga-Pflücker JC (2002) Induction of T cell development from hematopoietic progenitor cells by delta-like-1 in vitro. Immunity 17:749–756PubMedGoogle Scholar
  80. Shakib S, Desanti GE, Jenkinson WE, Parnell SM, Jenkinson EJ, Anderson G (2009) Checkpoints in the development of thymic cortical epithelial cells. J Immunol 182:130–137PubMedGoogle Scholar
  81. Shinkura R, Kitada K, Matsuda F, Tashiro K, Ikuta K, Suzuki M, Kogishi K, Serikawa T, Honjo T (1999) Alymphoplasia is caused by a point mutation in the mouse gene encoding Nf-κb-inducing kinase. Nat Genet 22:74–77PubMedGoogle Scholar
  82. Shortman K, Scollay R, Andrews P, Boyd R (1986) Development of T lymphocytes within the thymus and within thymic nurse cells. Curr Top Microbiol Immunol 126:5–18PubMedGoogle Scholar
  83. Su D, Ellis S, Napier A, Lee K, Manley NR (2001) Hoxa3 and Pax1 regulate epithelial cell death and proliferation during thymus and parathyroid organogenesis. Dev Biol 236:316–329PubMedGoogle Scholar
  84. Takahama Y, Letterio JJ, Suzuki H, Farr AG, Singer A (1994) Early progression of thymocytes along the CD4/CD8 developmental pathway is regulated by a subset of thymic epithelial cells expressing transforming growth factor β. J Exp Med 179:1495–1506PubMedGoogle Scholar
  85. Takahama Y, Nitta T, Mat Ripen A, Nitta S, Murata S, Tanaka K (2010) Role of thymic cortex-specific self-peptides in positive selection of T cells. Sem Immunol 22:287–293Google Scholar
  86. Takahama Y, Takada K, Murata S, Tanaka K (2012) β5t-containing thymoproteasome: specific expression in thymic cortical epithelial cells and role in positive selection of CD8+ T cells. Curr Opin Immunol 24:92–98PubMedGoogle Scholar
  87. Thompson PK, Zúñiga-Pflücker JC (2011) On becoming a T cell, a convergence of factors kick it up a Notch along the way. Semin Immunol 23:350–359PubMedGoogle Scholar
  88. Tousaint-Demylle D, Scheiff JM, Haumount S (1990) Thymic nurse cells: morphological study during their isolation from murine thymus. Cell Tissue Res 261:115–123Google Scholar
  89. van de Wijngaert FP, Rademakers LH, Schuurman HJ, de Weger RA, Kater L (1983) Identification and in situ localization of the “thymic nurse cell” in man. J Immunol 130:2348–2351PubMedGoogle Scholar
  90. van Ewijk W, Shores EW, Singer A (1994) Crosstalk in the mouse thymus. Immunol Today 15:214–217PubMedGoogle Scholar
  91. Viret C, Lamare C, Guiraud M, Fazilleau N, Bour A, Malissen B, Carrier A, Guerder S (2011a) Thymus-specific serine protease contributes to the diversification of the functional endogenous CD4 T cell receptor repertoire. J Exp Med 208:3–11PubMedGoogle Scholar
  92. Viret C, Leung-Theung-Long S, Serre L, Lamare C, Vignali DA, Malissen B, Carrier A, Guerder S (2011b) Thymus-specific serine protease controls autoreactive CD4 T cell development and autoimmune diabetes in mice. J Clin Invest 121:1810–1821PubMedGoogle Scholar
  93. von Freeden-Jeffry U, Solvason N, Howard M, Murray R (1997) The earliest T lineage-committed cells depend on IL-7 for Bcl-2 expression and normal cell cycle progression. Immunity 7:147–154Google Scholar
  94. Wada H, Masuda K, Satoh R, Kakugawa K, Ikawa T, Katsura Y, Kawamoto H (2008) Adult T-cell progenitors retain myeloid potential. Nature 452:768–772PubMedGoogle Scholar
  95. Weiner L, Han R, Scicchitano BM, Li J, Hasegawa K, Grossi M, Lee D, Brissette JL (2007) Dedicated epithelial recipient cells determine pigmentation patterns. Cell 130:932–942PubMedGoogle Scholar
  96. Wekerle H, Ketelson UP (1980) Thymic nurse cells. Ia-bearing epithelium involved in T-lymphocyte differentiation? Nature 283:402–404PubMedGoogle Scholar
  97. Wekerle H, Ketelson UP, Ernst M (1980) Thymic nurse cells. lymphoepithelial cell complexes in murine thymuses: morphological and serological characterization. J Exp Med 151:925–944PubMedGoogle Scholar
  98. Wick G, Rieker T, Penninger J (1991) Thymic nurse cells: a site for positive selection and differentiation of T cells. Curr Top Microbiol Immunol 173:99–105PubMedGoogle Scholar
  99. Wilson A, MacDonald HR, Radtke F (2001) Notch 1-deficient common lymphoid precursors adopt a B cell fate in the thymus. J Exp Med 194:1003–1012PubMedGoogle Scholar
  100. Wolfer A, Wilson A, Nemir M, MacDonald HR, Radtke F (2002) Inactivation of Notch1 impairs VDJ beta rearrangement and allows pre-TCR-independent survival of early alpha beta lineage thymocytes. Immunity 16:869–879PubMedGoogle Scholar
  101. Yamasaki S, Saito T (2007) Molecular basis for pre-TCR-mediated autonomous signaling. Trends Immunol 28:39–43PubMedGoogle Scholar
  102. Yang SJ, Ahn S, Park CS, Holmes KL, Westrup J, Chang CH, Kim MG (2006) The quantitative assessment of MHC II on thymic epithelium: implications in cortical thymocyte development. Int Immunol 18:729–739PubMedGoogle Scholar
  103. Zamisch M, Moore-Scott B, Su D, Lucas PJ, Manley N, Richie ER (2005) Ontogeny and regulation of IL-7-expressing thymic epithelial cells. J Immunol 174:60–67PubMedGoogle Scholar
  104. Zou D, Silvius D, Davenport J, Grifone R, Maire P, Xu PX (2006) Patterning of the third pharyngeal pouch into thymus/parathyroid by Six and Eya1. Dev Biol 293:499–512PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Kensuke Takada
    • 1
  • Izumi Ohigashi
    • 1
  • Michiyuki Kasai
    • 1
  • Hiroshi Nakase
    • 1
  • Yousuke Takahama
    • 1
    Email author
  1. 1.Division of Experimental ImmunologyInstitute for Genome Research, University of TokushimaTokushimaJapan

Personalised recommendations