γδ T Cells in Immunoregulation

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Regulatory T Cells and Clinical Application
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Abstract

The regulatory function of γδ T cells has not been appreciated until recently. In murine epithelial tissues, dendritic epidermal γδ T cells (DETCs) play a critical regulatory function in skin tissue surveillance and wound repair. It has been shown that this process is mediated by direct lyses of stressed or damaged keratinocytes via a cell-cell contact dependent mechanism. DETC-derived cytokines such as keratinocyte growth factor-1/2 and insulin-like growth factor-1 have also involved in regulating the processes of tissue repair, keratinocyte proliferation and survival, migration and recruitment of inflammatory cells. Moreover, DETCs can directly down-regulate cutaneous inflammation, promote wound healing, and protect against cutaneous malignancy. In humans, Vδ1 cells in tumor-infiltrating lymphocytes (TIL) from human breast cancer have been shown to possess an inhibitory effect on αβ T cells and dendritic cells in a soluble factor-dependent manner. Such immunosuppressive activity could be reversed by human Toll-like receptor 8 ligands both in-vitro and in-vivo, indicating that a unique TLR8 signaling pathway is involved in suppression of regulatory γδ1 TILs. More questions regarding the regulatory functions and the mechanism of suppression of γδ T cells need to be addressed in future studies, and these answers may have important implications in γδ T cell-based adoptive therapy for the treatment of cancers in clinic.

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References

  1. Tonegawa, S. Somatic generation of antibody diversity. Nature 302:575–581. (1983).

    Article  PubMed  CAS  Google Scholar 

  2. Hayday, A. C. γδ cells: A right time and a right place for a conserved third way of protection. Annu Rev Immunol 18:975–1026. (2000).

    Article  PubMed  CAS  Google Scholar 

  3. Brenner, M.B., McLean, J., Dialynas, D.P., Strominger, J.L., Smith, J.A., Owen, F.L., Seidman, J.G., Ip, S., Rosen, F., and Krangel, M.S. Identification of a putative second T-cell receptor. Nature 322:145–149. (1986).

    Article  PubMed  CAS  Google Scholar 

  4. Brandes M, Willimann K, Moser B. Professional antigen-presentation function by human γδ T cells. Science 309:264–268. (2005).

    Article  PubMed  CAS  Google Scholar 

  5. Born WK, Reardon CL, O'Brien RL. The function of gammadelta T cells in innate immunity. Curr Opin Immunol 18(1):31–38. (2006).

    Article  PubMed  CAS  Google Scholar 

  6. Bergstresser PR, Tigelaar RE, Dees JH, Streilein JW. Thy-1 antigen-bearing dendritic cells populate murine epidermis. J Invest Dermatol 81:286–288. (1983).

    Article  PubMed  CAS  Google Scholar 

  7. Tschachler E, Schuler G, Hutterer J, Leibl H, Wolff K, Stingl G. Expression of Thy-1 antigen by murine epidermal cells. J Invest Dermatol 81:282–285. (1983).

    Article  PubMed  CAS  Google Scholar 

  8. Asarnow DM, Kuziel WA, Bonyhadi M, Tigelaar RE, Tucker PW, Allison JP. Limited diversity of gamma/delta antigen receptor genes of Thy-1+ dendritic epidermal cells. Cell 55:837–847. (1988).

    Article  PubMed  CAS  Google Scholar 

  9. Heilig JS, Tonegawa S. Diversity of murine γ genes and expression in fetal and adult lymphocytes. Nature 322:836–840. (1986).

    Article  PubMed  CAS  Google Scholar 

  10. Havran WL, Allison JP. Origin of Thy-1+ dendritic epidermal cells of adult mice from fetal thymic precursors. Nature 344:68–70. (1990).

    Article  PubMed  CAS  Google Scholar 

  11. Payer E, Elbe A, Stingl G. Circulating CD3+/T cell receptor V γ3+ fetal murine thymocytes home to the skin and give rise to proliferating dendritic epidermal cells. J Immunol 146:2536–2543. (1991).

    PubMed  CAS  Google Scholar 

  12. Bandeira A, Itohara S, Bonneville M, Burlen-Defranoux O, Mota-Santos T, Coutinho A, Tonegawa S. Extrathymic origin of intestinal intraepithelial T cells bearing the γδ T cell receptor. Proc Natl Acad Sci USA 88:43–47. (1991).

    Article  PubMed  CAS  Google Scholar 

  13. Havran WL, Chien Y-H, Allison JP. Recognition of self antigens by skin-derived T cells with invariant γδ antigen receptors. Science 252:1430–1432. (1991).

    Article  PubMed  CAS  Google Scholar 

  14. Lewis JM, Tigelaar RE. Recognition of an epidermal stress antigen by murine γδ dendritic epidermal T cells (DETC). J Invest Dermatol 96:538A. (1991).

    Google Scholar 

  15. Jameson JM, Cauvi G, Witherden DA, Havran WL. A keratinocyte-responsive γδ TCR is necessary for dendritic epidermal T cell activation by damaged keratinocytes and maintenance in the epidermis. J Immunol 172:3573–3579. (2004).

    PubMed  CAS  Google Scholar 

  16. Jameson, J. et al. A role for skin γδ T cells in wound repair. Science 296:747–749. (2002).

    Article  PubMed  CAS  Google Scholar 

  17. Girardi, M. et al. Regulation of cutaneous malignancy by γδ T cells. Science 294:605–609. (2001).

    Article  PubMed  CAS  Google Scholar 

  18. Girardi, M. et al. The distinct contributions of murine T cell receptor (TCR) γδ + and TCR αβ+ T cells to different stages of chemically induced skin cancer. J Exp Med 198:747–755. (2003).

    Article  PubMed  CAS  Google Scholar 

  19. Boismenu R, Havran WL. Modulation of epithelial cell growth by intraepithelial γδ T cells. Science 266:1253–1255. (1994).

    Article  PubMed  CAS  Google Scholar 

  20. Sharp LL, Jameson JM, Cauvi G, Havran WL. Dendritic epidermal T cells regulate skin homeostasis through local production of insulin-like growth factor 1. Nat Immunol 6:73–79. (2005).

    Article  PubMed  CAS  Google Scholar 

  21. Boismenu R, Hobbs MV, Boullier S, Havran WL. Molecular and cellular biology of dendritic epidermal T cells. Semin Immunol 8:323–331. (1996).

    Article  PubMed  CAS  Google Scholar 

  22. Boismenu R, Feng L, **a YY, Chang JCC, Havran WL. Chemokine expression by intraepithelial γδ T cells: Implications for the recruitment of inflammatory cells to damaged epithelia. J Immunol 157:985–992. (1996).

    PubMed  CAS  Google Scholar 

  23. Jameson JM, Cauvi G, Sharp LL, Witherden DA, Havran WL. γδ T cell-induced hyaluronan production by epithelial cells regulates inflammation. J Exp Med 201:1269–1279. (2005).

    Article  PubMed  CAS  Google Scholar 

  24. Girardi, M. et al. Resident skin-specific γδ T cells provide local, nonredundant regulation of cutaneous inflammation. J Exp Med 195:855–867. (2002).

    Article  PubMed  CAS  Google Scholar 

  25. Holtmeier W, Pfander M, Hennemann A, Zollner TM, Kaufmann R, Caspary WF. The TCR-δ repertoire in normal human skin is restricted and distinct from the TCR-δ repertoire in the peripheral blood. J Invest Dermatol 116:275–280. (2001).

    Article  PubMed  CAS  Google Scholar 

  26. Hinz T, Wesch D, Halary F, Marx S, Choudhary A, Arden B, Janssen O, Bonneville M, Kabelitz D.Identifi cation of the complete expressed human T-cell receptor Vγ repertoire by flow cytometry. Int Immunol 9:1065–1072. (1997).

    Article  PubMed  CAS  Google Scholar 

  27. Porcelli SA, Brenner MB, Band H. Biology of the human γδ T-cell receptor. Immunol Rev 120:137–183. (1991).

    Article  PubMed  CAS  Google Scholar 

  28. Deusch K, Luling F, Reich K, Classen M, Wagner H, Pfeffer K. A major fraction of human intraepithelial lymphocytes simultaneously expresses the γ/δ T cell receptor, the CD8 accessory molecule and preferentially uses the Vδ1 gene segment. Eur J Immunol 21:1053–1059. (1991).

    Article  PubMed  CAS  Google Scholar 

  29. Holtmeier W. Compartmentalization of γ/δ T cells and their putative role in mucosal immunity. Crit Rev Immunol 23:473–488. (2003).

    Article  PubMed  Google Scholar 

  30. Modlin, R.L., Pirmez, C., Hofman, F.M., Torigian, V., Uyemura, K., Rea, T.H., Bloom, B.R., and Brenner, M.B. Lymphocytes bearing antigen-specific gamma delta T-cell receptors accumulate in human infectious disease lesions. Nature 339:544–548. (1989).

    Article  PubMed  CAS  Google Scholar 

  31. Constant, P., Davodeau, F., Peyrat, MA, Poquet, Y., Puzo, G., Bonne¬ville, M., and Fournie, J.J. Stimulation of human gamma delta T cells by nonpeptidic mycobacterial ligands. Science 264:267–270. (1994).

    Article  PubMed  CAS  Google Scholar 

  32. Bukowski, J.F., Morita, C.T., and Brenner, M.B. Human gamma delta T cells recognize alkylamines derived from microbes, edible plants, and tea: Implications for innate immunity. Immunity 11:57–65. (1999).

    Article  PubMed  CAS  Google Scholar 

  33. Groh, V., Steinle, A., Bauer, S., and Spies, T. Recognition of stress-induced MHC molecules by intestinal epithelial gammadelta T cells. Science 279:1737–1740. (1998).

    Article  PubMed  CAS  Google Scholar 

  34. Jameson, J., Witherden, D., and Havran, W.L. T-cell effector mechanisms: Gammadelta and CD1d-restricted subsets. Curr Opin Immunol 15:349–353. (2003).

    Article  PubMed  CAS  Google Scholar 

  35. Hayday, A, and Tigelaar, R. Immunoregulation in the tissues by gammadelta T cells. Nat Rev Immunol 3:233–242. (2003).

    Article  PubMed  CAS  Google Scholar 

  36. Pennington, D.J., Vermijlen, D., Wise, E.L, Clarke, S.L., Tigelaar, R.E., and Hayday, A.C. The integration of conventional and uncon¬ventional T cells that characterizes cell-mediated responses. Adv Immunol 87:27–59. (2005).

    Article  PubMed  CAS  Google Scholar 

  37. Ke Y., Kapp, L. M. and Kapp J.A. Inhibition of tumor rejection by γδ T cells and IL-10. Cell immunol 221:107–114. (2003).

    Article  PubMed  CAS  Google Scholar 

  38. Peng G, Wang HY, Peng W, Kiniwa Y, Seo KH, Wang RF. Tumor-infiltrating gammadelta T cells suppress T and dendritic cell function via mechanisms controlled by a unique toll-like receptor signaling pathway. Immunity 27(2):334–48. (2007).

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Wei He .

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Tang, L., Kang, N., He, W. (2008). γδ T Cells in Immunoregulation. In: Jiang, S. (eds) Regulatory T Cells and Clinical Application. Springer, New York, NY. https://doi.org/10.1007/978-0-387-77909-6_30

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