Advertisement

Seminars in Immunopathology

, Volume 32, Issue 3, pp 227–238 | Cite as

Dynamics of dendritic cell–T cell interactions: a role in T cell outcome

  • Stéphanie HuguesEmail author
Review

Abstract

Antigen-specific dendritic cells (DC)–T cell encounters occur in lymph nodes (LNs) and are essential for the induction of both priming and tolerance. In both cases, T cells are rapidly activated and proliferate. However, the subsequent outcome of T cell activation depends on the modulation of different DC- and T cell-intrinsic signals. Recent advances in two-photon (2P) microscopy have furthered our understanding regarding the complex choreography of DCs and T cells in intact LNs, and established differences in the dynamics of DC–T cell contacts during priming and tolerance induction. The mechanisms that favour DC–T cell encounters, as well as the contribution of the frequency and the duration of such encounters in dictating the T cell response, are discussed in this review.

Keywords

Dendritic cells T cells Dynamic interactions Priming Tolerance Lymph node 

Notes

Acknowledgements

The author thanks W. Ferlin, C. Ody and W. Reith for the critical reading of this manuscript. This work is supported by the Swiss National Science Foundation (grant 310030–127042).

References

  1. 1.
    Adler AJ, Marsh DW, Yochum GS, Guzzo JL, Nigam A, Nelson WG, Pardoll DM (1998) CD4+ T cell tolerance to parenchymal self-antigens requires presentation by bone marrow-derived antigen-presenting cells. J Exp Med 187:1555–1564PubMedCrossRefGoogle Scholar
  2. 2.
    Bonifaz L, Bonnyay D, Mahnke K, Rivera M, Nussenzweig MC, Steinman RM (2002) Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in the steady state leads to antigen presentation on major histocompatibility complex class I products and peripheral CD8+ T cell tolerance. J Exp Med 196:1627–1638PubMedCrossRefGoogle Scholar
  3. 3.
    Hawiger D, Inaba K, Dorsett Y, Guo M, Mahnke K, Rivera M, Ravetch JV, Steinman RM, Nussenzweig MC (2001) Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J Exp Med 194:769–779PubMedCrossRefGoogle Scholar
  4. 4.
    Hernandez J, Aung S, Redmond WL, Sherman LA (2001) Phenotypic and functional analysis of CD8(+) T cells undergoing peripheral deletion in response to cross-presentation of self-antigen. J Exp Med 194:707–717PubMedCrossRefGoogle Scholar
  5. 5.
    Liu K, Iyoda T, Saternus M, Kimura Y, Inaba K, Steinman RM (2002) Immune tolerance after delivery of dying cells to dendritic cells in situ. J Exp Med 196:1091–1097PubMedCrossRefGoogle Scholar
  6. 6.
    Probst HC, Lagnel J, Kollias G, van den Broek M (2003) Inducible transgenic mice reveal resting dendritic cells as potent inducers of CD8+ T cell tolerance. Immunity 18:713–720PubMedCrossRefGoogle Scholar
  7. 7.
    Sakaguchi S (2004) Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 22:531–562PubMedCrossRefGoogle Scholar
  8. 8.
    Misra N, Bayry J, Lacroix-Desmazes S, Kazatchkine MD, Kaveri SV (2004) Cutting edge: human CD4+CD25+ T cells restrain the maturation and antigen-presenting function of dendritic cells. J Immunol 172:4676–4680PubMedGoogle Scholar
  9. 9.
    Albert ML (2004) Death-defying immunity: do apoptotic cells influence antigen processing and presentation? Nat Rev Immunol 4:223–231PubMedCrossRefGoogle Scholar
  10. 10.
    Gunzer M, Schafer A, Borgmann S, Grabbe S, Zanker KS, Brocker EB, Kampgen E, Friedl P (2000) Antigen presentation in extracellular matrix: interactions of T cells with dendritic cells are dynamic, short lived, and sequential. Immunity 13:323–332PubMedCrossRefGoogle Scholar
  11. 11.
    Iezzi G, Karjalainen K, Lanzavecchia A (1998) The duration of antigenic stimulation determines the fate of naive and effector T cells. Immunity 8:89–95PubMedCrossRefGoogle Scholar
  12. 12.
    van Stipdonk MJ, Lemmens EE, Schoenberger SP (2001) Naive CTLs require a single brief period of antigenic stimulation for clonal expansion and differentiation. Nat Immunol 2:423–429PubMedGoogle Scholar
  13. 13.
    Benvenuti F, Lagaudriere-Gesbert C, Grandjean I, Jancic C, Hivroz C, Trautmann A, Lantz O, Amigorena S (2004) Dendritic cell maturation controls adhesion, synapse formation, and the duration of the interactions with naive T lymphocytes. J Immunol 172:292–301PubMedGoogle Scholar
  14. 14.
    Bousso P, Robey E (2003) Dynamics of CD8+ T cell priming by dendritic cells in intact lymph nodes. Nat Immunol 4:579–585PubMedCrossRefGoogle Scholar
  15. 15.
    Mempel TR, Henrickson SE, Von Andrian UH (2004) T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature 427:154–159PubMedCrossRefGoogle Scholar
  16. 16.
    Miller MJ, Wei SH, Parker I, Cahalan MD (2002) Two-photon imaging of lymphocyte motility and antigen response in intact lymph node. Science 296:1869–1873PubMedCrossRefGoogle Scholar
  17. 17.
    Stoll S, Delon J, Brotz TM, Germain RN (2002) Dynamic imaging of T cell–dendritic cell interactions in lymph nodes. Science 296:1873–1876PubMedCrossRefGoogle Scholar
  18. 18.
    Cahalan MD, Parker I, Wei SH, Miller MJ (2002) Two-photon tissue imaging: seeing the immune system in a fresh light. Nat Rev Immunol 2:872–880PubMedCrossRefGoogle Scholar
  19. 19.
    Germain RN, Miller MJ, Dustin ML, Nussenzweig MC (2006) Dynamic imaging of the immune system: progress, pitfalls and promise. Nat Rev Immunol 6:497–507PubMedCrossRefGoogle Scholar
  20. 20.
    Bousso P (2008) T-cell activation by dendritic cells in the lymph node: lessons from the movies. Nat Rev Immunol 8:675–684PubMedCrossRefGoogle Scholar
  21. 21.
    Bajenoff M, Egen JG, Koo LY, Laugier JP, Brau F, Glaichenhaus N, Germain RN (2006) Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes. Immunity 25:989–1001PubMedCrossRefGoogle Scholar
  22. 22.
    Lindquist RL, Shakhar G, Dudziak D, Wardemann H, Eisenreich T, Dustin ML, Nussenzweig MC (2004) Visualizing dendritic cell networks in vivo. Nat Immunol 5:1243–1250PubMedCrossRefGoogle Scholar
  23. 23.
    Miller MJ, Hejazi AS, Wei SH, Cahalan MD, Parker I (2004) T cell repertoire scanning is promoted by dynamic dendritic cell behavior and random T cell motility in the lymph node. Proc Natl Acad Sci USA 101:998–1003PubMedCrossRefGoogle Scholar
  24. 24.
    Shakhar G, Lindquist RL, Skokos D, Dudziak D, Huang JH, Nussenzweig MC, Dustin ML (2005) Stable T cell–dendritic cell interactions precede the development of both tolerance and immunity in vivo. Nat Immunol 6:707–714PubMedCrossRefGoogle Scholar
  25. 25.
    Liu YJ (2005) IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu Rev Immunol 23:275–306PubMedCrossRefGoogle Scholar
  26. 26.
    Cavanagh LL, Weninger W (2008) Dendritic cell behaviour in vivo: lessons learned from intravital two-photon microscopy. Immunol Cell Biol 86:428–438PubMedCrossRefGoogle Scholar
  27. 27.
    Hugues S, Scholer A, Boissonnas A, Nussbaum A, Combadiere C, Amigorena S, Fetler L (2007) Dynamic imaging of chemokine-dependent CD8+ T cell help for CD8+ T cell responses. Nat Immunol 8:921–930PubMedCrossRefGoogle Scholar
  28. 28.
    Scholer A, Hugues S, Boissonnas A, Fetler L, Amigorena S (2008) Intercellular adhesion molecule-1-dependent stable interactions between T cells and dendritic cells determine CD8+ T cell memory. Immunity 28:258–270PubMedCrossRefGoogle Scholar
  29. 29.
    Celli S, Lemaitre F, Bousso P (2007) Real-time manipulation of T cell–dendritic cell interactions in vivo reveals the importance of prolonged contacts for CD4+ T cell activation. Immunity 27:625–634PubMedCrossRefGoogle Scholar
  30. 30.
    Shortman K, Naik SH (2007) Steady-state and inflammatory dendritic-cell development. Nat Rev Immunol 7:19–30PubMedCrossRefGoogle Scholar
  31. 31.
    Allan RS, Waithman J, Bedoui S, Jones CM, Villadangos JA, Zhan Y, Lew AM, Shortman K, Heath WR, Carbone FR (2006) Migratory dendritic cells transfer antigen to a lymph node-resident dendritic cell population for efficient CTL priming. Immunity 25:153–162PubMedCrossRefGoogle Scholar
  32. 32.
    Carbone FR, Belz GT, Heath WR (2004) Transfer of antigen between migrating and lymph node-resident DCs in peripheral T-cell tolerance and immunity. Trends Immunol 25:655–658PubMedCrossRefGoogle Scholar
  33. 33.
    Miller MJ, Safrina O, Parker I, Cahalan MD (2004) Imaging the single cell dynamics of CD4+ T cell activation by dendritic cells in lymph nodes. J Exp Med 200:847–856PubMedCrossRefGoogle Scholar
  34. 34.
    Hugues S, Fetler L, Bonifaz L, Helft J, Amblard F, Amigorena S (2004) Distinct T cell dynamics in lymph nodes during the induction of tolerance and immunity. Nat Immunol 5:1235–1242PubMedCrossRefGoogle Scholar
  35. 35.
    Odoardi F, Kawakami N, Li Z, Cordiglieri C, Streyl K, Nosov M, Klinkert WE, Ellwart JW, Bauer J, Lassmann H et al (2007) Instant effect of soluble antigen on effector T cells in peripheral immune organs during immunotherapy of autoimmune encephalomyelitis. Proc Natl Acad Sci USA 104:920–925PubMedCrossRefGoogle Scholar
  36. 36.
    Tang Q, Adams JY, Tooley AJ, Bi M, Fife BT, Serra P, Santamaria P, Locksley RM, Krummel MF, Bluestone JA (2006) Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice. Nat Immunol 7:83–92PubMedCrossRefGoogle Scholar
  37. 37.
    Hickman HD, Takeda K, Skon CN, Murray FR, Hensley SE, Loomis J, Barber GN, Bennink JR, Yewdell JW (2008) Direct priming of antiviral CD8+ T cells in the peripheral interfollicular region of lymph nodes. Nat Immunol 9:155–165PubMedCrossRefGoogle Scholar
  38. 38.
    Filipe-Santos O, Pescher P, Breart B, Lippuner C, Aebischer T, Glaichenhaus N, Spath GF, Bousso P (2009) A dynamic map of antigen recognition by CD4 T cells at the site of Leishmania major infection. Cell Host Microbe 6:23–33PubMedCrossRefGoogle Scholar
  39. 39.
    Sen D, Deerinck TJ, Ellisman MH, Parker I, Cahalan MD (2008) Quantum dots for tracking dendritic cells and priming an immune response in vitro and in vivo. PLoS ONE 3:e3290PubMedCrossRefGoogle Scholar
  40. 40.
    Colonna M, Trinchieri G, Liu YJ (2004) Plasmacytoid dendritic cells in immunity. Nat Immunol 5:1219–1226PubMedCrossRefGoogle Scholar
  41. 41.
    Villadangos JA, Young L (2008) Antigen-presentation properties of plasmacytoid dendritic cells. Immunity 29:352–361PubMedCrossRefGoogle Scholar
  42. 42.
    Di Pucchio T, Chatterjee B, Smed-Sorensen A, Clayton S, Palazzo A, Montes M, Xue Y, Mellman I, Banchereau J, Connolly JE (2008) Direct proteasome-independent cross-presentation of viral antigen by plasmacytoid dendritic cells on major histocompatibility complex class I. Nat Immunol 9:551–557PubMedCrossRefGoogle Scholar
  43. 43.
    Hoeffel G, Ripoche AC, Matheoud D, Nascimbeni M, Escriou N, Lebon P, Heshmati F, Guillet JG, Gannage M, Caillat-Zucman S et al (2007) Antigen crosspresentation by human plasmacytoid dendritic cells. Immunity 27:481–492PubMedCrossRefGoogle Scholar
  44. 44.
    Sapoznikov A, Fischer JA, Zaft T, Krauthgamer R, Dzionek A, Jung S (2007) Organ-dependent in vivo priming of naive CD4+, but not CD8+, T cells by plasmacytoid dendritic cells. J Exp Med 204:1923–1933PubMedCrossRefGoogle Scholar
  45. 45.
    Young LJ, Wilson NS, Schnorrer P, Proietto A, ten Broeke T, Matsuki Y, Mount AM, Belz GT, O’Keeffe M, Ohmura-Hoshino M et al (2008) Differential MHC class II synthesis and ubiquitination confers distinct antigen-presenting properties on conventional and plasmacytoid dendritic cells. Nat Immunol 9:1244–1252PubMedCrossRefGoogle Scholar
  46. 46.
    Yoneyama H, Matsuno K, Zhang Y, Nishiwaki T, Kitabatake M, Ueha S, Narumi S, Morikawa S, Ezaki T, Lu B et al (2004) Evidence for recruitment of plasmacytoid dendritic cell precursors to inflamed lymph nodes through high endothelial venules. Int Immunol 16:915–928PubMedCrossRefGoogle Scholar
  47. 47.
    Ochando JC, Homma C, Yang Y, Hidalgo A, Garin A, Tacke F, Angeli V, Li Y, Boros P, Ding Y et al (2006) Alloantigen-presenting plasmacytoid dendritic cells mediate tolerance to vascularized grafts. Nat Immunol 7:652–662PubMedCrossRefGoogle Scholar
  48. 48.
    Mittelbrunn M, Martinez Del Hoyo G, Lopez-Bravo M, Martin-Cofreces NB, Scholer A, Hugues S, Fetler L, Amigorena S, Ardavin C, Sanchez-Madrid F (2009) Imaging of plasmacytoid dendritic cell interactions with T cells. Blood 113:75–84PubMedCrossRefGoogle Scholar
  49. 49.
    Miller MJ, Wei SH, Cahalan MD, Parker I (2003) Autonomous T cell trafficking examined in vivo with intravital two-photon microscopy. Proc Natl Acad Sci USA 100:2604–2609PubMedCrossRefGoogle Scholar
  50. 50.
    Cyster JG (1999) Chemokines and cell migration in secondary lymphoid organs. Science 286:2098–2102PubMedCrossRefGoogle Scholar
  51. 51.
    Worbs T, Mempel TR, Bolter J, von Andrian UH, Forster R (2007) CCR7 ligands stimulate the intranodal motility of T lymphocytes in vivo. J Exp Med 204:489–495PubMedCrossRefGoogle Scholar
  52. 52.
    Gretz JE, Anderson AO, Shaw S (1997) Cords, channels, corridors and conduits: critical architectural elements facilitating cell interactions in the lymph node cortex. Immunol Rev 156:11–24PubMedCrossRefGoogle Scholar
  53. 53.
    Kaldjian EP, Gretz JE, Anderson AO, Shi Y, Shaw S (2001) Spatial and molecular organization of lymph node T cell cortex: a labyrinthine cavity bounded by an epithelium-like monolayer of fibroblastic reticular cells anchored to basement membrane-like extracellular matrix. Int Immunol 13:1243–1253PubMedCrossRefGoogle Scholar
  54. 54.
    Katakai T, Hara T, Sugai M, Gonda H, Shimizu A (2004) Lymph node fibroblastic reticular cells construct the stromal reticulum via contact with lymphocytes. J Exp Med 200:783–795PubMedCrossRefGoogle Scholar
  55. 55.
    Jacobelli J, Bennett FC, Pandurangi P, Tooley AJ, Krummel MF (2009) Myosin-IIA and ICAM-1 regulate the interchange between two distinct modes of T cell migration. J Immunol 182:2041–2050PubMedCrossRefGoogle Scholar
  56. 56.
    Tooley AJ, Gilden J, Jacobelli J, Beemiller P, Trimble WS, Kinoshita M, Krummel MF (2009) Amoeboid T lymphocytes require the septin cytoskeleton for cortical integrity and persistent motility. Nat Cell Biol 11:17–26PubMedCrossRefGoogle Scholar
  57. 57.
    Cahalan MD, Parker I (2008) Choreography of cell motility and interaction dynamics imaged by two-photon microscopy in lymphoid organs. Annu Rev Immunol 26:585–626PubMedCrossRefGoogle Scholar
  58. 58.
    Asperti-Boursin F, Real E, Bismuth G, Trautmann A, Donnadieu E (2007) CCR7 ligands control basal T cell motility within lymph node slices in a phosphoinositide 3-kinase-independent manner. J Exp Med 204:1167–1179PubMedCrossRefGoogle Scholar
  59. 59.
    Wei SH, Safrina O, Yu Y, Garrod KR, Cahalan MD, Parker I (2007) Ca2+ signals in CD4+ T cells during early contacts with antigen-bearing dendritic cells in lymph node. J Immunol 179:1586–1594PubMedGoogle Scholar
  60. 60.
    Fischer UB, Jacovetty EL, Medeiros RB, Goudy BD, Zell T, Swanson JB, Lorenz E, Shimizu Y, Miller MJ, Khoruts A et al (2007) MHC class II deprivation impairs CD4 T cell motility and responsiveness to antigen-bearing dendritic cells in vivo. Proc Natl Acad Sci USA 104:7181–7186PubMedCrossRefGoogle Scholar
  61. 61.
    Friedman RS, Jacobelli J, Krummel MF (2006) Surface-bound chemokines capture and prime T cells for synapse formation. Nat Immunol 7:1101–1108PubMedCrossRefGoogle Scholar
  62. 62.
    Beuneu H, Garcia Z, Bousso P (2006) Cutting edge: cognate CD4 help promotes recruitment of antigen-specific CD8 T cells around dendritic cells. J Immunol 177:1406–1410PubMedGoogle Scholar
  63. 63.
    Castellino F, Huang AY, Altan-Bonnet G, Stoll S, Scheinecker C, Germain RN (2006) Chemokines enhance immunity by guiding naive CD8+ T cells to sites of CD4+ T cell-dendritic cell interaction. Nature 440:890–895PubMedCrossRefGoogle Scholar
  64. 64.
    Benvenuti F, Hugues S, Walmsley M, Ruf S, Fetler L, Popoff M, Tybulewicz VL, Amigorena S (2004) Requirement of Rac1 and Rac2 expression by mature dendritic cells for T cell priming. Science 305:1150–1153PubMedCrossRefGoogle Scholar
  65. 65.
    Skokos D, Shakhar G, Varma R, Waite JC, Cameron TO, Lindquist RL, Schwickert T, Nussenzweig MC, Dustin ML (2007) Peptide-MHC potency governs dynamic interactions between T cells and dendritic cells in lymph nodes. Nat Immunol 8:835–844PubMedCrossRefGoogle Scholar
  66. 66.
    Celli S, Garcia Z, Bousso P (2005) CD4 T cells integrate signals delivered during successive DC encounters in vivo. J Exp Med 202:1271–1278PubMedCrossRefGoogle Scholar
  67. 67.
    Henrickson SE, Mempel TR, Mazo IB, Liu B, Artyomov MN, Zheng H, Peixoto A, Flynn MP, Senman B, Junt T et al (2008) T cell sensing of antigen dose governs interactive behavior with dendritic cells and sets a threshold for T cell activation. Nat Immunol 9:282–291PubMedCrossRefGoogle Scholar
  68. 68.
    Dustin ML, Tseng SY, Varma R, Campi G (2006) T cell-dendritic cell immunological synapses. Curr Opin Immunol 18:512–516PubMedCrossRefGoogle Scholar
  69. 69.
    Grakoui A, Bromley SK, Sumen C, Davis MM, Shaw AS, Allen PM, Dustin ML (1999) The immunological synapse: a molecular machine controlling T cell activation. Science 285:221–227PubMedCrossRefGoogle Scholar
  70. 70.
    Dustin ML, Chan AC (2000) Signaling takes shape in the immune system. Cell 103:283–294PubMedCrossRefGoogle Scholar
  71. 71.
    Obst R, van Santen HM, Mathis D, Benoist C (2005) Antigen persistence is required throughout the expansion phase of a CD4(+) T cell response. J Exp Med 201:1555–1565PubMedCrossRefGoogle Scholar
  72. 72.
    Costello PS, Gallagher M, Cantrell DA (2002) Sustained and dynamic inositol lipid metabolism inside and outside the immunological synapse. Nat Immunol 3:1082–1089PubMedCrossRefGoogle Scholar
  73. 73.
    Curtsinger JM, Johnson CM, Mescher MF (2003) CD8 T cell clonal expansion and development of effector function require prolonged exposure to antigen, costimulation, and signal 3 cytokine. J Immunol 171:5165–5171PubMedGoogle Scholar
  74. 74.
    Fabre S, Lang V, Harriague J, Jobart A, Unterman TG, Trautmann A, Bismuth G (2005) Stable activation of phosphatidylinositol 3-kinase in the T cell immunological synapse stimulates Akt signaling to FoxO1 nuclear exclusion and cell growth control. J Immunol 174:4161–4171PubMedGoogle Scholar
  75. 75.
    Harriague J, Bismuth G (2002) Imaging antigen-induced PI3K activation in T cells. Nat Immunol 3:1090–1096PubMedCrossRefGoogle Scholar
  76. 76.
    Schrum AG, Turka LA (2002) The proliferative capacity of individual naive CD4(+) T cells is amplified by prolonged T cell antigen receptor triggering. J Exp Med 196:793–803PubMedCrossRefGoogle Scholar
  77. 77.
    Bhakta NR, Oh DY, Lewis RS (2005) Calcium oscillations regulate thymocyte motility during positive selection in the three-dimensional thymic environment. Nat Immunol 6:143–151PubMedCrossRefGoogle Scholar
  78. 78.
    Negulescu PA, Krasieva TB, Khan A, Kerschbaum HH, Cahalan MD (1996) Polarity of T cell shape, motility, and sensitivity to antigen. Immunity 4:421–430PubMedCrossRefGoogle Scholar
  79. 79.
    Molon B, Gri G, Bettella M, Gomez-Mouton C, Lanzavecchia A, Martinez AC, Manes S, Viola A (2005) T cell costimulation by chemokine receptors. Nat Immunol 6:465–471PubMedCrossRefGoogle Scholar
  80. 80.
    Sims TN, Soos TJ, Xenias HS, Dubin-Thaler B, Hofman JM, Waite JC, Cameron TO, Thomas VK, Varma R, Wiggins CH et al (2007) Opposing effects of PKCtheta and WASp on symmetry breaking and relocation of the immunological synapse. Cell 129:773–785PubMedCrossRefGoogle Scholar
  81. 81.
    Faure S, Salazar-Fontana LI, Semichon M, Tybulewicz VL, Bismuth G, Trautmann A, Germain RN, Delon J (2004) ERM proteins regulate cytoskeleton relaxation promoting T cell-APC conjugation. Nat Immunol 5:272–279PubMedCrossRefGoogle Scholar
  82. 82.
    Walunas TL, Lenschow DJ, Bakker CY, Linsley PS, Freeman GJ, Green JM, Thompson CB, Bluestone JA (1994) CTLA-4 can function as a negative regulator of T cell activation. Immunity 1:405–413PubMedCrossRefGoogle Scholar
  83. 83.
    Schneider H, Downey J, Smith A, Zinselmeyer BH, Rush C, Brewer JM, Wei B, Hogg N, Garside P, Rudd CE (2006) Reversal of the TCR stop signal by CTLA-4. Science 313:1972–1975PubMedCrossRefGoogle Scholar
  84. 84.
    Downey J, Smith A, Schneider H, Hogg N, Rudd CE (2008) TCR/CD3 mediated stop-signal is decoupled in T-cells from Ctla4 deficient mice. Immunol Lett 115:70–72PubMedCrossRefGoogle Scholar
  85. 85.
    Fife BT, Pauken KE, Eagar TN, Obu T, Wu J, Tang Q, Azuma M, Krummel MF, Bluestone JA (2009) Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal. Nat Immunol 10:1185–1192PubMedCrossRefGoogle Scholar
  86. 86.
    Pulecio J, Tagliani E, Scholer A, Prete F, Fetler L, Burrone OR, Benvenuti F (2008) Expression of Wiskott-Aldrich syndrome protein in dendritic cells regulates synapse formation and activation of naive CD8+ T cells. J Immunol 181:1135–1142PubMedGoogle Scholar
  87. 87.
    Dustin ML, Bivona TG, Philips MR (2004) Membranes as messengers in T cell adhesion signaling. Nat Immunol 5:363–372PubMedCrossRefGoogle Scholar
  88. 88.
    Chang JT, Palanivel VR, Kinjyo I, Schambach F, Intlekofer AM, Banerjee A, Longworth SA, Vinup KE, Mrass P, Oliaro J et al (2007) Asymmetric T lymphocyte division in the initiation of adaptive immune responses. Science 315:1687–1691PubMedCrossRefGoogle Scholar
  89. 89.
    Kedl RM, Schaefer BC, Kappler JW, Marrack P (2002) T cells down-modulate peptide-MHC complexes on APCs in vivo. Nat Immunol 3:27–32PubMedCrossRefGoogle Scholar
  90. 90.
    Garcia Z, Pradelli E, Celli S, Beuneu H, Simon A, Bousso P (2007) Competition for antigen determines the stability of T cell-dendritic cell interactions during clonal expansion. Proc Natl Acad Sci USA 104:4553–4558PubMedCrossRefGoogle Scholar
  91. 91.
    Jelley-Gibbs DM, Dibble JP, Filipson S, Haynes L, Kemp RA, Swain SL (2005) Repeated stimulation of CD4 effector T cells can limit their protective function. J Exp Med 201:1101–1112PubMedCrossRefGoogle Scholar
  92. 92.
    Steinman RM, Hawiger D, Liu K, Bonifaz L, Bonnyay D, Mahnke K, Iyoda T, Ravetch J, Dhodapkar M, Inaba K et al (2003) Dendritic cell function in vivo during the steady state: a role in peripheral tolerance. Ann NY Acad Sci 987:15–25PubMedCrossRefGoogle Scholar
  93. 93.
    Gunzer M, Weishaupt C, Hillmer A, Basoglu Y, Friedl P, Dittmar KE, Kolanus W, Varga G, Grabbe S (2004) A spectrum of biophysical interaction modes between T cells and different antigen-presenting cells during priming in 3-D collagen and in vivo. Blood 104:2801–2809PubMedCrossRefGoogle Scholar
  94. 94.
    Probst HC, McCoy K, Okazaki T, Honjo T, van den Broek M (2005) Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4. Nat Immunol 6:280–286PubMedCrossRefGoogle Scholar
  95. 95.
    Garside P, Brewer JM (2008) Real-time imaging of the cellular interactions underlying tolerance, priming, and responses to infection. Immunol Rev 221:130–146PubMedCrossRefGoogle Scholar
  96. 96.
    Zinselmeyer BH, Dempster J, Gurney AM, Wokosin D, Miller M, Ho H, Millington OR, Smith KM, Rush CM, Parker I et al (2005) In situ characterization of CD4+ T cell behavior in mucosal and systemic lymphoid tissues during the induction of oral priming and tolerance. J Exp Med 201:1815–1823PubMedCrossRefGoogle Scholar
  97. 97.
    Bakocevic N, Worbs T, Davalos-Misslitz A, Forster R (2010) T cell-dendritic cell interaction dynamics during the induction of respiratory tolerance and immunity. J Immunol 184:1317–1327PubMedCrossRefGoogle Scholar
  98. 98.
    Tadokoro CE, Shakhar G, Shen S, Ding Y, Lino AC, Maraver A, Lafaille JJ, Dustin ML (2006) Regulatory T cells inhibit stable contacts between CD4+ T cells and dendritic cells in vivo. J Exp Med 203:505–511PubMedCrossRefGoogle Scholar
  99. 99.
    Rush CM, Millington OR, Hutchison S, Bryson K, Brewer JM, Garside P (2009) Characterization of CD4+ T-cell–dendritic cell interactions during secondary antigen exposure in tolerance and priming. Immunology 128:463–471PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Department of PathologyUniversity of Geneva Medical SchoolGenevaSwitzerland

Personalised recommendations