Skip to main content
SpringerLink
Log in

A role for epithelial γδ T cells in tissue repair

  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

My colleagues and I have a long-term interest in interactions between intraepithelial γδ T cells and neighboring epithelial cells. We have focused our studies on interactions in the thymus, skin, and intestine, and are investigating the development, specificity, and function of these γδ T cells. Our results have defined unique properties of these cells and support a specialized role for epithelial γδ T cells in immune surveillance, wound repair, inflammation, and protection from malignancy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Chien YH, Jores R, Crowley M: Recognition by γδ T cells. Annu Rev Immunol 1996;14:511–532.

    Article  PubMed  CAS  Google Scholar 

  2. Kaufmann SHE: γ/δ and other unconventional T lymphocytes: what do they see and what do they do?. Proc Natl Acad Sci USA 1996;93:2272–2279.

    Article  PubMed  CAS  Google Scholar 

  3. Allison JP, Havran WL: The immunobiology of T cells with invariant γδ antigen receptors. Annu Rev Immunol 1991;9: 679–705.

    PubMed  CAS  Google Scholar 

  4. Havran WL, Boismenu R: Activation and function of γδ T cells. Curr Opin Immunol 1994;6:442–446.

    Article  PubMed  CAS  Google Scholar 

  5. Boismenu R, Havran WL: γδ T cells in host defense and epithelial cell biology. Clin Immunol Immunopathol 1998;86:121–133.

    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 1983;81:286–288.

    Article  PubMed  CAS  Google Scholar 

  7. Stingl G, Koning F, Yamada H, Yokoyama WM, Tschachler E, Bluestone JA, Steiner G, Samelson LE, Lew AM, Coligan JE, Shevach EM: Thy-1+dendritic epidermal cells express T3 antigen and the T-cell receptor gamma chain. Proc Natl Acad Sci USA 1987;84:4586–4590.

    Article  PubMed  CAS  Google Scholar 

  8. Bergstresser PD, Cruz PD, Takashima A: Dendritic epidermal T cells: lessons from mice for humans. J Invest Dermatol 1993; 100:80S-83S.

    Article  PubMed  CAS  Google Scholar 

  9. Tigelaar RE, Lewis JM: Immunobiology of mouse dendritic epidermal T cells: a decadelater, some answers but still more questions. J Invest Dermatol 1995;105: 43S-49S.

    Article  PubMed  CAS  Google Scholar 

  10. Boismenu R, Hobbs MV, Boullier S, Havran WL: Molecular and cellular biology of dendritic epidermal T cells. Semin Immunol 1997;8:323–331.

    Article  Google Scholar 

  11. Asarnow DM, Kuziel WA, Bonyhadi M, Tigelaar RE, Tucker PW, Allison JP: Limited diversity of γδ antigen receptor genes of thy-1+ dendritic epidermal cells. Cell 1988;55:837–847.

    Article  PubMed  CAS  Google Scholar 

  12. Asarnow D, Goodman T, LeFrancois L, Allison JP: Distinc tantigen receptor repertoi reso of two classes of murine epithelium-associated T cells. Nature 1989;341:60–62.

    Article  PubMed  CAS  Google Scholar 

  13. Havran WL, Grell S, Duwe G, Kimura J, Wilson A, Kruisbeek AM, O'Brien RL, Bom W, Tigelaar RE, Allison JP: Limited diversity of T-cell receptor γ-chain expression of murine Thy-1+dendritic epidermal cells revealed by Vγ3-specific monoclonal antibody. Proc Natl Acad Sci USA 1989;86:4185–4189.

    Article  PubMed  CAS  Google Scholar 

  14. Havran WL, Allison JP: Developmentally ondered appearance of thymocytes expressing different T cell antigen receptors. Nature 1988;335:443–445.

    Article  PubMed  CAS  Google Scholar 

  15. Itohara S, Farr AG, Lafaille JJ, Bonneville M, Takagaki Y, Haas W, Tonegawa S: Homing of a gamma/delta thymocyte subset with homogenous T-cell receptors to mucosal epithelia. Nature 1990;343:754–757.

    Article  PubMed  CAS  Google Scholar 

  16. Haas W, Pereira P, Tonegawa S: Gamma/delta cells. Annu Rev Immunol 1993;11:637–685.

    PubMed  CAS  Google Scholar 

  17. Schild H, Mavaddat N, Litzenberger C, Ehrich E, Davis M, Bluestone J, Matis L, Draper R, Chien Y: The nature of major histocompatibility complex recognition by γδ T cells. Cell 1994;76:29–37.

    Article  PubMed  CAS  Google Scholar 

  18. Rock EP, Sibbald PR, Davis MM, Chien Y-H: CDR3 length in antigen-specific immune receptors. J Exp Med 1994;179:323–328.

    Article  PubMed  CAS  Google Scholar 

  19. Havran WL, Chien Y-H, Allison JP: Recognition of self antigens by skin-derived T cells with invariant gamma/delta antigen receptors. Science 1991;252:1430–1432.

    Article  PubMed  CAS  Google Scholar 

  20. Maeurer MJ, Martin D, Walter W, Liu K, Zitvogel L, Halusczcak K, Rabinowich H, Duquesnoy R, Storkus W, Lotze M: Human intestinal Vδ1+T lymphocytes recognize tumor cells of epithelial origin. J Exp Med 1996;183: 1681–1696.

    Article  PubMed  CAS  Google Scholar 

  21. Groh V, Rhinehart R, Secrist H, Bauer S, Grabstein KH, Spies T: Broad tumor-associated expression and recognition by tumor-derived γδ T cells of MICA and MICB. Proc Natl Acad Sci USA 1999;96:6879–6884.

    Article  PubMed  CAS  Google Scholar 

  22. Heyborne K, Fu Y, Nelson A, Farr A, O'Brien R, Born W: Recognition of trophoblasts by γδT cells. J Immunol 1994;153:2918–2926.

    PubMed  CAS  Google Scholar 

  23. O'Brien R, Born W: Heat shock proteins as antigens for γδT cells. Semin Immunol 1991;3:81–87.

    PubMed  Google Scholar 

  24. Constant P, Davodeau F, Peyral M-A, Poquet Y, Puzo G, Bonneville M, Fournie J-J: Stimulation of human γδ T cells by nonpeptidic mycobacterial ligands. Science 1994;264:267–270.

    Article  PubMed  CAS  Google Scholar 

  25. Tanaka Y, Sano S, Nieves E, De Libeno G, Rosa D, Modlin RL, Brenner MB, Bloom BR, Morita CT: Nonpeptide ligands for human γδT cells. Proc Natl Acad Sci USA 1994;91:8175–8179.

    Article  PubMed  CAS  Google Scholar 

  26. Tanaka Y, Morita CT, Nieves E, Brenner MB, Bloom BR: Natural and synthetic non-peptide antigens recognized by human γδ T cells. Nature 1995;375:155–158.

    Article  PubMed  CAS  Google Scholar 

  27. Morita CT, Beckman EM, Bukowski JF, Tanaka Y, Band H, Bloom BR, Golan DE, Brenner MB: Direct presentation of non-peptide prenyl pyrophosphate antigens to human γδT cells. Immunity 1995;3:495–507.

    Article  PubMed  CAS  Google Scholar 

  28. Lang F, Peyrat MA, Constant P, Davodeau F, David-Ameline J, Poquet Y, Vie H, Fournie JJ, Bonneville M: Early activation of human Vγ9Vδ2T cell broad cytotoxicity and TNF production by nonpeptidic mycobacterial ligands. J Immunol 1995;154: 5986–5994.

    PubMed  CAS  Google Scholar 

  29. Huber H, Descossy P, van Brandwijk R, Knop J: Activation of murine epidermal γδ+ cells by keratinocytes treated with contact sensitizers. J Immunol 1995;155:2888–2894.

    PubMed  CAS  Google Scholar 

  30. Correa I, Bix M, Liao N-S, Zijlstra M, Jaenisch R, Raulet D: T cells bearing γδ T cell receptors velop normally in β2-microglobulinmutant mice. Proc Natl Acad Sci USA 1992;89:653–657.

    Article  PubMed  CAS  Google Scholar 

  31. Cosgnove D, Gray D, Dierich A, Kaufman J, Lemeur M, Benoist C, Mathis D: Mice lacking MHC Class II molecules. Cell 1991;66: 1051–1066.

    Article  Google Scholar 

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

    Google Scholar 

  33. Kaminski MJ, Bergstresser, PR, Takashima A: In vivo activation of mouse dendritic epidermal T cells in sites of contact dermatitis. Eur J Immunol 1993;23: 1715–1718.

    Article  PubMed  CAS  Google Scholar 

  34. Kaminski MJ, Cruz PD, Bergstresser PR, Takashima A: Killing of skin-derived tumor cells by mouse dendritic epidermal T cells. Cancer Research 1993;53: 4014–4019.

    PubMed  CAS  Google Scholar 

  35. Mallick-Wood CA, Lewis JM, Richie LI, Owen MJ, Tigelaar RE, Hayday AC: Conservation of T cell receptor conformation in epidermal γδ cells with disrupted primary Vγ gene usage. Science 1998;279: 1729–1733.

    Article  PubMed  CAS  Google Scholar 

  36. Rotzschke O, Falk K, Deres K, Schild H, Nord M, Metzger J, Jung G, Rammensee H-G: Isolation and analysis of naturally processed viral peptides as recognized by cytotoxic T cells. Nature 1990;347:252–254.

    Article  Google Scholar 

  37. Falk K, Rotzschke O, Stevanovic S, Jung G, Rammersee HG: Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature 1991;351:290–296.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  39. Werner S: Keratinocyte growth factor: a unique player in epithelial repair processes. Cytokine Growth Factor Rev 1998;9: 153–165.

    Article  PubMed  CAS  Google Scholar 

  40. Werner S, Peters KG, Longaker MT, Fuller-Pace F, Banda MJ, Williams LT: Large induction of keratinocyte growth factor rexpression in the dermis during wound healing. Proc Natl Acad Sci USA 1992;89:6896–6900.

    Article  PubMed  CAS  Google Scholar 

  41. Werner S, Smola H, Liao X, Longaker M, Krieg T, Hofschneider P, Williams LT: The function of KGF in morphogenesis of epithelium and reepithelialization of wounds. Science 1994;266:819–822.

    Article  PubMed  CAS  Google Scholar 

  42. Staiano-Coico L, Krueger JG, Rubin JS, D'limi S, Vallat VP, Valentino L, Fabey T Hawes A, Kingston G, Madden MR, Mathwich M, Gottlieb AH, Aaronson SA: Human keratinocyte growth factor effects in a porcine model of epidenmal wound healing. J Exp Med 1993;178:865–878.

    Article  PubMed  CAS  Google Scholar 

  43. Pierce GF, Yanagihara D, Klopchin K, Danilenko DM, Hsu E, Kenney WC, Morris CF: Stimulation of all epithelial elements during skin regeneration by keratinocyte growth factor. J Exp Med 1994; 179:831–840.

    Article  PubMed  CAS  Google Scholar 

  44. Danilenko DM, Ring BD, Tarpley JE, Morris B, Van GY, Morawiecki A, Callahan W, Goldenberg M, Hershenson S, Pierce GF: Growth factor in porcine full and partial thickness burn repair. Differing targets and effects of keratinocyte growth factor, platelet-derived growth factor-BB, epidermal growth factor, and neu differentiation factor. Am J Pathol 1995; 147:1261–1277.

    PubMed  CAS  Google Scholar 

  45. Wu L, Pierce GF, Galiano RD, Mustoe TA: Keratinocyte growth factor induces granulation tissue in ischemic dermal wounds: importance of epithelial-mesenc hymal cell interactions. Arch Surg 1996; 131:660–666.

    PubMed  CAS  Google Scholar 

  46. Guo L, Degenstein L, Fuchs E: Keratinocyte growth factor is required for hair development but not for wound healing. Genes Dev 1996;10:165–175.

    PubMed  CAS  Google Scholar 

  47. Yamasaki M, Miyake A, Tagashira S, Itoh N: Structure and expression of the rat mRNA encoding a novel member of the fibroblast growth factor family. J Biol Chem 1996; 271:15,918–15,921.

    CAS  Google Scholar 

  48. Beer HD, Florence C, Dammeier J, McGuire L, Werner S, Duan DR: Mouse fibro blast growth factor 10: cDNA cloning, protein characterization, and regulation of mRNA expression. Oncogene 1997;15: 2211–2218.

    Article  PubMed  CAS  Google Scholar 

  49. Sekine K, Ohuchi H, Fujiwara M, Yamasaki M, Yoshizawa T, Sato T, Yagishita N, Matsui D, Koga Y, Itoh N, Kato S: FGF10 is essential for limb and lung formation. Nat Genetics 1999;21:138–141.

    Article  CAS  Google Scholar 

  50. Min H, Danilenko DM, Scully SA, Bolon B, Ring BD, Tarpley JE, DeRose M, Simonet WS: FGF-10 is required for both limb and lung development and exhibits striking functional similarity to Drosophila branchless. Genes Dev 1998;12: 3156–3161.

    PubMed  CAS  Google Scholar 

  51. Boismenu R, Feng L, Xia YY, Chang JCC, Havran WL: Chemokine expression by intra epithelial γδ T cells: implications for the recruitment of inflammatory cells

Download references

Author information

Author notes

  1. Wendy L. Havran

    Present address: Department of Immunology, IMMS, The Scripps Research Institute, 10550 N. TorreyPines Road, 92037, La Jolh, CA

Authors and Affiliations

    Authors
    1. Wendy L. Havran
      View author publications

      You can also search for this author in PubMed Google Scholar

    Rights and permissions

    Reprints and permissions

    About this article

    Cite this article

    Havran, W.L. A role for epithelial γδ T cells in tissue repair. Immunol Res 21, 63–69 (2000). https://doi.org/10.1385/IR:21:2-3:63

    Download citation

    • Issue Date:

    • DOI: https://doi.org/10.1385/IR:21:2-3:63

    Key words

    Search

    Navigation