Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Regional and mucosal memory T cells

Abstract

After infection, most antigen-specific memory T cells reside in nonlymphoid tissues. Tissue-specific programming during priming leads to directed migration of T cells to the appropriate tissue, which promotes the development of tissue-resident memory in organs such as intestinal mucosa and skin. Mechanisms that regulate the retention of tissue-resident memory T cells include transforming growth factor-β (TGF-β)-mediated induction of the E-cadherin receptor CD103 and downregulation of the chemokine receptor CCR7. These pathways enhance protection in internal organs, such as the nervous system, and in the barrier tissues—the mucosa and skin. Memory T cells that reside at these surfaces provide a first line of defense against subsequent infection, and defining the factors that regulate their development is critical to understanding organ-based immunity.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The migration of effector and memory T cells to sites of localized infection.
Figure 2: The generation of a diverse and dynamic memory T cell population is a highly orchestrated process.
Figure 3: Multifaceted roles of TGF-β in generating mucosal effector and memory T cell populations.

Similar content being viewed by others

References

  1. Starr, T.K., Jameson, S.C. & Hogquist, K.A. Positive and negative selection of T cells. Annu. Rev. Immunol. 21, 139–176 (2003).

    Article  CAS  PubMed  Google Scholar 

  2. Hamann, D. et al. Phenotypic and functional separation of memory and effector human CD8+ T cells. J. Exp. Med. 186, 1407–1418 (1997).

    CAS  PubMed Central  PubMed  Google Scholar 

  3. Sallusto, F., Lenig, D., Forster, R., Lipp, M. & Lanzavecchia, A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 401, 708–712 (1999).

    Article  CAS  PubMed  Google Scholar 

  4. Reinhardt, R.L., Khoruts, A., Merica, R., Zell, T. & Jenkins, M.K. Visualizing the generation of memory CD4 T cells in the whole body. Nature 410, 101–105 (2001).

    CAS  PubMed  Google Scholar 

  5. Masopust, D., Vezys, V., Marzo, A.L. & Lefrançois, L. Preferential localization of effector memory cells in nonlymphoid tissue. Science 291, 2413–2417 (2001).

    CAS  PubMed  Google Scholar 

  6. Masopust, D. et al. Activated primary and memory CD8 T cells migrate to nonlymphoid tissues regardless of site of activation or tissue of origin. J. Immunol. 172, 4875–4882 (2004).

    CAS  PubMed  Google Scholar 

  7. Klonowski, K.D. et al. Dynamics of blood-borne CD8 memory T cell migration in vivo. Immunity 20, 551–562 (2004).

    CAS  PubMed  Google Scholar 

  8. Zammit, D.J., Turner, D.L., Klonowski, K.D., Lefrançois, L. & Cauley, L.S. Residual antigen presentation after influenza virus infection affects CD8 T cell activation and migration. Immunity 24, 439–449 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Marzo, A.L., Yagita, H. & Lefrançois, L. Cutting edge: migration to nonlymphoid tissues results in functional conversion of central to effector memory CD8 T cells. J. Immunol. 179, 36–40 (2007).

    CAS  PubMed  Google Scholar 

  10. Lee, Y.-T. et al. Environmental and antigen receptor-derived signals support sustained surveillance of the lungs by pathogen-specific cytotoxic T lymphocytes. J. Virol. 85, 4085–4094 (2011).

    CAS  PubMed Central  PubMed  Google Scholar 

  11. Iwasaki, A. Antiviral immune responses in the genital tract: clues for vaccines. Nat. Rev. Immunol. 10, 699–711 (2010).

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Liu, L.M. & MacPherson, G.G. Antigen acquisition by dendritic cells: intestinal dendritic cells acquire antigen administered orally and can prime naive T cells in vivo. J. Exp. Med. 177, 1299–1307 (1993).

    CAS  PubMed  Google Scholar 

  13. Huang, F.-P. A discrete subpopulation of dendritic cells transports apoptotic intestinal epithelial cells to T cell areas of mesenteric lymph nodes. J. Exp. Med. 191, 435–444 (2000).

    CAS  PubMed Central  PubMed  Google Scholar 

  14. Yrlid, U., Jenkins, C.D. & MacPherson, G.G. Relationships between distinct blood monocyte subsets and migrating intestinal lymph dendritic cells in vivo under steady-state conditions. J. Immunol. 176, 4155–4162 (2006).

    CAS  PubMed  Google Scholar 

  15. Perdomo, O.J. et al. Acute inflammation causes epithelial invasion and mucosal destruction in experimental shigellosis. J. Exp. Med. 180, 1307–1319 (1994).

    CAS  PubMed  Google Scholar 

  16. Jones, B.D., Ghori, N. & Falkow, S. Salmonella typhimurium initiates murine infection by penetrating and destroying the specialized epithelial M cells of the Peyer′s patches. J. Exp. Med. 180, 15–23 (1994).

    CAS  PubMed  Google Scholar 

  17. Neutra, M.R., Frey, A. & Kraehenbuhl, J.P. Epithelial M cells: gateways for mucosal infection and immunization. Cell 86, 345–348 (1996).

    CAS  PubMed  Google Scholar 

  18. Salazar-Gonzalez, R.M. et al. CCR6-mediated dendritic cell activation of pathogen-specific T cells in Peyer′s patches. Immunity 24, 623–632 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Teitelbaum, R. et al. The M cell as a portal of entry to the lung for the bacterial pathogen Mycobacterium tuberculosis. Immunity 10, 641–650 (1999).

    CAS  PubMed  Google Scholar 

  20. Jang, M.H. et al. Intestinal villous M cells: an antigen entry site in the mucosal epithelium. Proc. Natl. Acad. Sci. USA 101, 6110–6115 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Schubert, W.D. et al. Structure of internalin, a major invasion protein of Listeria monocytogenes, in complex with its human receptor E-cadherin. Cell 111, 825–836 (2002).

    CAS  PubMed  Google Scholar 

  22. Disson, O. et al. Modeling human listeriosis in natural and genetically engineered animals. Nat. Protoc. 4, 799–810 (2009).

    CAS  PubMed  Google Scholar 

  23. Lefrançois, L. & Obar, J.J. Once a killer, always a killer: from cytotoxic T cell to memory cell. Immunol. Rev. 235, 206–218 (2010).

    PubMed Central  PubMed  Google Scholar 

  24. Obar, J.J. & Lefrançois, L. Early events governing memory CD8+ T-cell differentiation. Int. Immunol. 22, 619–625 (2010).

    CAS  PubMed Central  PubMed  Google Scholar 

  25. Obar, J.J. & Lefrançois, L. Early signals during CD8+ T cell priming regulate the generation of central memory cells. J. Immunol. 185, 263–272 (2010).

    CAS  PubMed  Google Scholar 

  26. Schluns, K.S., Kieper, W.C., Jameson, S.C. & Lefrançois, L. Interleukin-7 mediates the homeostasis of naive and memory CD8 T cells in vivo. Nat. Immunol. 1, 426–432 (2000).

    CAS  PubMed  Google Scholar 

  27. Kaech, S.M. et al. Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nat. Immunol. 4, 1191–1198 (2003).

    CAS  PubMed  Google Scholar 

  28. Joshi, N.S. et al. Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor. Immunity 27, 281–295 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sarkar, S. et al. Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates. J. Exp. Med. 205, 625–640 (2008).

    CAS  PubMed Central  PubMed  Google Scholar 

  30. Klonowski, K.D., Williams, K.J., Marzo, A.L. & Lefrançois, L. Cutting edge: IL-7-independent regulation of IL-7 receptor α expression and memory CD8 T cell development. J. Immunol. 177, 4247–4251 (2006).

    CAS  PubMed  Google Scholar 

  31. Hand, T.W., Morre, M. & Kaech, S.M. Expression of IL-7 receptor α is necessary but not sufficient for the formation of memory CD8 T cells during viral infection. Proc. Natl. Acad. Sci. USA 104, 11730–11735 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Haring, J.S. et al. Constitutive expression of IL-7 receptor α does not support increased expansion or prevent contraction of antigen-specific CD4 or CD8 T cells following Listeria monocytogenes infection. J. Immunol. 180, 2855–2862 (2008).

    CAS  PubMed  Google Scholar 

  33. Sanjabi, S., Mosaheb, M.M. & Flavell, R.A. Opposing effects of TGF-β and IL-15 cytokines control the number of short-lived effector CD8+ T cells. Immunity 31, 131–144 (2009).

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Obar, J.J. et al. CD4+ T cell regulation of CD25 expression controls development of short-lived effector CD8+ T cells in primary and secondary responses. Proc. Natl. Acad. Sci. USA 107, 193–198 (2010).

    CAS  PubMed  Google Scholar 

  35. Cui, W., Joshi, N.S., Jiang, A. & Kaech, S.M. Effects of Signal 3 during CD8 T cell priming: bystander production of IL-12 enhances effector T cell expansion but promotes terminal differentiation. Vaccine 27, 2177–2187 (2009).

    CAS  PubMed Central  PubMed  Google Scholar 

  36. Sheridan, B.S., Cherpes, T.L., Urban, J., Kalinski, P. & Hendricks, R.L. Reevaluating the CD8 T-cell response to herpes simplex virus type 1: involvement of CD8 T cells reactive to subdominant epitopes. J. Virol. 83, 2237–2245 (2009).

    CAS  PubMed  Google Scholar 

  37. Croom, H.A. et al. Memory precursor phenotype of CD8+ T cells reflects early antigenic experience rather than memory numbers in a model of localized acute influenza infection. Eur. J. Immunol. 41, 682–693 (2011).

    CAS  PubMed  Google Scholar 

  38. Tripp, R.A., Hou, S. & Doherty, P.C. Temporal loss of the activated L-selectin-low phenotype for virus-specific CD8+ memory T cells. J. Immunol. 154, 5870–5875 (1995).

    CAS  PubMed  Google Scholar 

  39. Wherry, E.J. et al. Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat. Immunol. 4, 225–234 (2003).

    CAS  PubMed  Google Scholar 

  40. Marzo, A.L. et al. Initial T cell frequency dictates memory CD8+ T cell lineage commitment. Nat. Immunol. 6, 793–799 (2005).

    CAS  PubMed Central  PubMed  Google Scholar 

  41. Woodland, D.L. & Kohlmeier, J.E. Migration, maintenance and recall of memory T cells in peripheral tissues. Nat. Rev. Immunol. 9, 153–161 (2009).

    CAS  PubMed  Google Scholar 

  42. Lefrançois, L. & Puddington, L. Intestinal and pulmonary mucosal T cells: local heroes fight to maintain the status quo. Annu. Rev. Immunol. 24, 681–704 (2006).

    PubMed  Google Scholar 

  43. Lefrançois, L. Development, trafficking, and function of memory T-cell subsets. Immunol. Rev. 211, 93–103 (2006).

    PubMed  Google Scholar 

  44. Klonowski, K.D. et al. CD8 T cell recall responses are regulated by the tissue tropism of the memory cell and pathogen. J. Immunol. 177, 6738–6746 (2006).

    CAS  PubMed  Google Scholar 

  45. Crowe, S.R. et al. Differential antigen presentation regulates the changing patterns of CD8+ T cell immunodominance in primary and secondary influenza virus infections. J. Exp. Med. 198, 399–410 (2003).

    CAS  PubMed Central  PubMed  Google Scholar 

  46. Hufford, M.M., Kim, T.S., Sun, J. & Braciale, T.J. Antiviral CD8+ T cell effector activities in situ are regulated by target cell type. J. Exp. Med. 208, 167–180 (2011).

    CAS  PubMed Central  PubMed  Google Scholar 

  47. Wakim, L.M., Waithman, J., van Rooijen, N., Heath, W.R. & Carbone, F.R. Dendritic cell-induced memory T cell activation in nonlymphoid tissues. Science 319, 198–202 (2008).

    CAS  PubMed  Google Scholar 

  48. Freeman, M.L., Sheridan, B.S., Bonneau, R.H. & Hendricks, R.L. Psychological stress compromises CD8+ T cell control of latent herpes simplex virus type 1 infections. J. Immunol. 179, 322–328 (2007).

    CAS  PubMed  Google Scholar 

  49. Himmelein, S. et al. Circulating herpes simplex type 1 (HSV-1)-specific CD8+ T cells do not access HSV-1 latently infected trigeminal ganglia. Herpesviridae 2, 5 (2011).

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Gebhardt, T. et al. Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus. Nat. Immunol. 10, 524–530 (2009).

    CAS  PubMed  Google Scholar 

  51. Mora, J.R. et al. Selective imprinting of gut-homing T cells by Peyer′s patch dendritic cells. Nature 424, 88–93 (2003).

    CAS  PubMed  Google Scholar 

  52. Agace, W. Generation of gut-homing T cells and their localization to the small intestinal mucosa. Immunol. Lett. 128, 21–23 (2010).

    CAS  PubMed  Google Scholar 

  53. Campbell, D.J. & Butcher, E.C. Rapid acquisition of tissue-specific homing phenotypes by CD4+ T cells activated in cutaneous or mucosal lymphoid tissues. J. Exp. Med. 195, 135–141 (2002).

    CAS  PubMed Central  PubMed  Google Scholar 

  54. Mora, J.R. et al. Reciprocal and dynamic control of CD8 T cell homing by dendritic cells from skin- and gut-associated lymphoid tissues. J. Exp. Med. 201, 303–316 (2005).

    CAS  PubMed Central  PubMed  Google Scholar 

  55. Iwata, M. et al. Retinoic acid imprints gut-homing specificity on T cells. Immunity 21, 527–538 (2004).

    CAS  PubMed  Google Scholar 

  56. Svensson, M. et al. Retinoic acid receptor signaling levels and antigen dose regulate gut homing receptor expression on CD8+ T cells. Mucosal Immunol. 1, 38–48 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Lefrançois, L. et al. The role of β7 integrins in CD8 T cell trafficking during an antiviral immune response. J. Exp. Med. 189, 1631–1638 (1999).

    PubMed Central  PubMed  Google Scholar 

  58. Hamann, A., Andrew, D.P., Jablonski-Westrich, D., Holzmann, B. & Butcher, E.C. Role of a4-integrins in lymphocyte homing to mucosal tissues in vivo. J. Immunol. 152, 3282–3293 (1994).

    CAS  PubMed  Google Scholar 

  59. Svensson, M. et al. CCL25 mediates the localization of recently activated CD8αβ+ lymphocytes to the small-intestinal mucosa. J. Clin. Invest. 110, 1113–1121 (2002).

    CAS  PubMed Central  PubMed  Google Scholar 

  60. Sandborn, W.J. et al. Natalizumab induction and maintenance therapy for Crohn′s disease. N. Engl. J. Med. 353, 1912–1925 (2005).

    CAS  PubMed  Google Scholar 

  61. Feagan, B.G. et al. Treatment of ulcerative colitis with a humanized antibody to the α4β7 integrin. N. Engl. J. Med. 352, 2499–2507 (2005).

    CAS  PubMed  Google Scholar 

  62. Wurbel, M.A., Malissen, M., Guy-Grand, D., Malissen, B. & Campbell, J.J. Impaired accumulation of antigen-specific CD8 lymphocytes in chemokine CCL25-deficient intestinal epithelium and lamina propria. J. Immunol. 178, 7598–7606 (2007).

    CAS  PubMed  Google Scholar 

  63. Streeter, P.R., Berg, E.L., Rouse, B.T., Bargatze, R.F. & Butcher, E.C. A tissue-specific endothelial cell molecule involved in lymphocyte homing. Nature 331, 41–46 (1988).

    CAS  PubMed  Google Scholar 

  64. Berg, E.L. et al. Homing receptors and vascular addressins: cell adhesion molecules that direct lymphocyte traffic. Immunol. Rev. 108, 5–18 (1989).

    CAS  PubMed  Google Scholar 

  65. Briskin, M. et al. Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in intestinal tract and associated lymphoid tissue. Am. J. Pathol. 151, 97–110 (1997).

    CAS  PubMed Central  PubMed  Google Scholar 

  66. Soderberg, K.A., Linehan, M.M., Ruddle, N.H. & Iwasaki, A. MAdCAM-1 expressing sacral lymph node in the lymphotoxin β-deficient mouse provides a site for immune generation following vaginal herpes simplex virus-2 infection. J. Immunol. 173, 1908–1913 (2004).

    CAS  PubMed  Google Scholar 

  67. Bedoui, S. et al. Cross-presentation of viral and self antigens by skin-derived CD103+ dendritic cells. Nat. Immunol. 10, 488–495 (2009).

    CAS  PubMed  Google Scholar 

  68. Kim, T.S. & Braciale, T.J. Respiratory dendritic cell subsets differ in their capacity to support the induction of virus-specific cytotoxic CD8+ T cell responses. PLoS ONE 4, e4204 (2009).

    PubMed Central  PubMed  Google Scholar 

  69. Ballesteros-Tato, A., Leon, B., Lund, F.E. & Randall, T.D. Temporal changes in dendritic cell subsets, cross-priming and costimulation via CD70 control CD8+ T cell responses to influenza. Nat. Immunol. 11, 216–224 (2010).

    CAS  PubMed Central  PubMed  Google Scholar 

  70. del Rio, M.L., Bernhardt, G., Rodriguez-Barbosa, J.I. & Forster, R. Development and functional specialization of CD103+ dendritic cells. Immunol. Rev. 234, 268–281 (2010).

    CAS  PubMed  Google Scholar 

  71. Coombes, J.L. et al. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-β and retinoic acid-dependent mechanism. J. Exp. Med. 204, 1757–1764 (2007).

    CAS  PubMed Central  PubMed  Google Scholar 

  72. Sun, C.M. et al. Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J. Exp. Med. 204, 1775–1785 (2007).

    CAS  PubMed Central  PubMed  Google Scholar 

  73. Siddiqui, K.R., Laffont, S. & Powrie, F. E-cadherin marks a subset of inflammatory dendritic cells that promote T cell-mediated colitis. Immunity 32, 557–567 (2010).

    CAS  PubMed Central  PubMed  Google Scholar 

  74. Kim, S.K. et al. Generation of mucosal cytotoxic T cells against soluble protein by tissue-specific environmental and costimulatory signals. Proc. Natl. Acad. Sci. USA 95, 10814–10819 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Masopust, D. et al. Dynamic T cell migration program provides resident memory within intestinal epithelium. J. Exp. Med. 207, 553–564 (2010).

    CAS  PubMed Central  PubMed  Google Scholar 

  76. Kunkel, E.J. et al. Expression of the chemokine receptors CCR4, CCR5, and CXCR3 by human tissue-infiltrating lymphocytes. Am. J. Pathol. 160, 347–355 (2002).

    CAS  PubMed Central  PubMed  Google Scholar 

  77. Ely, K.H., Cookenham, T., Roberts, A.D. & Woodland, D.L. Memory T cell populations in the lung airways are maintained by continual recruitment. J. Immunol. 176, 537–543 (2006).

    CAS  PubMed  Google Scholar 

  78. Goodarzi, K., Goodarzi, M., Tager, A.M., Luster, A.D. & von Andrian, U.H. Leukotriene B4 and BLT1 control cytotoxic effector T cell recruitment to inflamed tissues. Nat. Immunol. 4, 965–973 (2003).

    CAS  PubMed  Google Scholar 

  79. Tager, A.M. et al. Leukotriene B4 receptor BLT1 mediates early effector T cell recruitment. Nat. Immunol. 4, 982–990 (2003).

    CAS  PubMed  Google Scholar 

  80. Richter, M. et al. Collagen distribution and expression of collagen-binding α1β1 (VLA-1) and α2β1 (VLA-2) integrins on CD4 and CD8 T cells during influenza infection. J. Immunol. 178, 4506–4516 (2007).

    CAS  PubMed  Google Scholar 

  81. Ray, S.J. et al. The collagen binding α1β1 integrin VLA-1 regulates CD8 T cell-mediated immune protection against heterologous influenza infection. Immunity 20, 167–179 (2004).

    CAS  PubMed  Google Scholar 

  82. Kim, S.K., Reed, D.S., Heath, W.R., Carbone, F. & Lefrançois, L. Activation and migration of CD8 T cells in the intestinal mucosa. J. Immunol. 159, 4295–4306 (1997).

    CAS  PubMed  Google Scholar 

  83. El-Asady, R. et al. TGFβ-dependent CD103 expression by CD8+ T cells promotes selective destruction of the host intestinal epithelium during graft-versus-host disease. J. Exp. Med. 201, 1647–1657 (2005).

    CAS  PubMed Central  PubMed  Google Scholar 

  84. Kim, S.K., Schluns, K.S. & Lefrançois, L. Induction and visualization of mucosal memory CD8 T cells following systemic virus infection. J. Immunol. 163, 4125–4132 (1999).

    CAS  PubMed  Google Scholar 

  85. Schön, M.P. et al. Mucosal T lymphocyte numbers are selectively reduced in integrin α E (CD103)-deficient mice. J. Immunol. 162, 6641–6649 (1999).

    PubMed  Google Scholar 

  86. Poussier, P., Edouard, P., Lee, C., Binnie, M. & Julius, M. Thymus-independent development and negative selection of T cells expressing T cell receptor α/β in the intestinal epithelium: evidence for distinct circulation patterns of gut- and thymus-derived T lymphocytes. J. Exp. Med. 176, 187–199 (1992).

    CAS  PubMed  Google Scholar 

  87. Wakim, L.M., Woodward-Davis, A. & Bevan, M.J. Memory T cells persisting within the brain after local infection show functional adaptations to their tissue of residence. Proc. Natl. Acad. Sci. USA 107, 17872–17879 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Khanna, K.M., Bonneau, R.H., Kinchington, P.R. & Hendricks, R.L. Herpes simplex virus-specific memory CD8+ T cells are selectively activated and retained in latently infected sensory ganglia. Immunity 18, 593–603 (2003).

    CAS  PubMed Central  PubMed  Google Scholar 

  89. Sheridan, B.S., Khanna, K.M., Frank, G.M. & Hendricks, R.L. Latent virus influences the generation and maintenance of CD8+ T cell memory. J. Immunol. 177, 8356–8364 (2006).

    CAS  PubMed  Google Scholar 

  90. Van Assche, G. et al. Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn′s disease. N. Engl. J. Med. 353, 362–368 (2005).

    CAS  PubMed  Google Scholar 

  91. Langer-Gould, A., Atlas, S.W., Green, A.J., Bollen, A.W. & Pelletier, D. Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N. Engl. J. Med. 353, 375–381 (2005).

    CAS  PubMed  Google Scholar 

  92. Kleinschmidt-DeMasters, B.K. & Tyler, K.L. Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon β-1a for multiple sclerosis. N. Engl. J. Med. 353, 369–374 (2005).

    CAS  PubMed  Google Scholar 

  93. Khanna, K.M. et al. In situ imaging reveals different responses by naive and memory CD8 T cells to late antigen presentation by lymph node DC after influenza virus infection. Eur. J. Immunol. 38, 3304–3315 (2008).

    CAS  PubMed Central  PubMed  Google Scholar 

  94. Shapiro, L. & Weis, W.I. Structure and biochemistry of cadherins and catenins. Cold Spring Harb. Perspect. Biol. 1, a003053 (2009).

    PubMed Central  PubMed  Google Scholar 

  95. Li, Y. et al. Structure of natural killer cell receptor KLRG1 bound to E-cadherin reveals basis for MHC-independent missing self recognition. Immunity 31, 35–46 (2009).

    PubMed Central  PubMed  Google Scholar 

  96. Lefrançois, L., Barrett, T.A., Havran, W.L. & Puddington, L. Developmental expression of the αIELβ7 integrin on T cell receptor γδ and T cell receptor αβ T cells. Eur. J. Immunol. 24, 635–640 (1994).

    PubMed  Google Scholar 

  97. Schlickum, S. et al. Integrin α E(CD103)β 7 influences cellular shape and motility in a ligand-dependent fashion. Blood 112, 619–625 (2008).

    CAS  PubMed  Google Scholar 

  98. Le Floc'h, A. αEβ7 integrin interaction with E-cadherin promotes antitumor CTL activity by triggering lytic granule polarization and exocytosis. J. Exp. Med. 204, 559–570 (2007).

    CAS  PubMed  Google Scholar 

  99. Feng, C. et al. A potential role for CD69 in thymocyte emigration. Int. Immunol. 14, 535–544 (2002).

    CAS  PubMed  Google Scholar 

  100. Shiow, L.R. et al. CD69 acts downstream of interferon-α/β to inhibit S1P1 and lymphocyte egress from lymphoid organs. Nature 440, 540–544 (2006).

    CAS  PubMed  Google Scholar 

  101. Bankovich, A.J., Shiow, L.R. & Cyster, J.G. CD69 suppresses sphingosine 1-phosophate receptor-1 (S1P1) function through interaction with membrane helix 4. J. Biol. Chem. 285, 22328–22337 (2010).

    CAS  PubMed Central  PubMed  Google Scholar 

  102. Debes, G.F. et al. Chemokine receptor CCR7 required for T lymphocyte exit from peripheral tissues. Nat. Immunol. 6, 889–894 (2005).

    CAS  PubMed Central  PubMed  Google Scholar 

  103. Bromley, S.K., Thomas, S.Y. & Luster, A.D. Chemokine receptor CCR7 guides T cell exit from peripheral tissues and entry into afferent lymphatics. Nat. Immunol. 6, 895–901 (2005).

    CAS  PubMed  Google Scholar 

  104. Amanna, I.J. & Slifka, M.K. Contributions of humoral and cellular immunity to vaccine-induced protection in humans. Virology 411, 206–215 (2011).

    CAS  PubMed  Google Scholar 

  105. Chakrabarti, L.A. & Simon, V. Immune mechanisms of HIV control. Curr. Opin. Immunol. 22, 488–496 (2010).

    CAS  PubMed Central  PubMed  Google Scholar 

  106. Streeck, H. & Nixon, D.F. T cell immunity in acute HIV-1 infection. J. Infect. Dis. 202 Suppl 2, S302–S308 (2010).

    CAS  PubMed  Google Scholar 

  107. Fontoura, P. Monoclonal antibody therapy in multiple sclerosis: Paradigm shifts and emerging challenges. MAbs 2, 670–681 (2010).

    PubMed Central  PubMed  Google Scholar 

  108. Reenaers, C., Louis, E. & Belaiche, J. Current directions of biologic therapies in inflammatory bowel disease. Therap. Adv. Gastroenterol. 3, 99–106 (2010).

    CAS  PubMed Central  PubMed  Google Scholar 

  109. Nakanishi, Y., Lu, B., Gerard, C. & Iwasaki, A. CD8+ T lymphocyte mobilization to virus-infected tissue requires CD4+ T-cell help. Nature 462, 510–513 (2009).

    CAS  PubMed Central  PubMed  Google Scholar 

  110. Kelsall, B.L. & Leon, F. Involvement of intestinal dendritic cells in oral tolerance, immunity to pathogens, and inflammatory bowel disease. Immunol. Rev. 206, 132–148 (2005).

    CAS  PubMed  Google Scholar 

  111. Taylor, B.C. et al. TSLP regulates intestinal immunity and inflammation in mouse models of helminth infection and colitis. J. Exp. Med. 206, 655–667 (2009).

    CAS  PubMed Central  PubMed  Google Scholar 

  112. Rubinstein, M.P. et al. IL-7 and IL-15 differentially regulate CD8+ T-cell subsets during contraction of the immune response. Blood 112, 3704–3712 (2008).

    CAS  PubMed Central  PubMed  Google Scholar 

  113. DePaolo, R.W. et al. Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens. Nature 471, 220–224 (2011).

    CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Brian S Sheridan or Leo Lefrançois.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sheridan, B., Lefrançois, L. Regional and mucosal memory T cells. Nat Immunol 12, 485–491 (2011). https://doi.org/10.1038/ni.2029

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ni.2029

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing