Skip to main content

Advertisement

SpringerLink
Log in

γδ T cells in autoimmunity

  • Published:
Springer Seminars in Immunopathology Aims and scope Submit manuscript

Conclusions

γδ T cells likely play a critical role in the host defenses, and recent evidence has indicated they are important in regulation of the immune response after pathogen challenge. Data are also accumulating that they play a part in autoimmunity and immune regulation. Evidence indicates that γδ T cells mediate these effects through cytokine production, via direct effects on cells of the adaptive immune response, or through interactions with innate immune components or barriers. Nevertheless, the biological function of γδ T cells in immune responses, especially in autoimmunity, largely remains unresolved. Further studies are needed to gain more knowledge about the immunobiology of these cells, asking why precisely they bear an activated phenotype in vivo, how their cytokine production is regulated, and how they interact with other cells of the innate and adaptive immune responses.

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.

Similar content being viewed by others

References

  1. Morita C, Verma S, Aparicio P, C M-A, Spits H, Brenner MB (1991) Functionally distinct subsets of human γ/δ T cells. Eur J Immunol 21:2999

    Article  PubMed  CAS  Google Scholar 

  2. King DP, Hyde DM, Jackson KA, Novosad DM, Ellis TN, Putney L, Srovall MY, Van Winkle LS, Beaman BL, Ferrick DA (1999) Cutting edge: protective response to pulmonary injury requires gamma delta T lymphocytes. J Immunol 162:5033

    PubMed  CAS  Google Scholar 

  3. Morita CT, Beckman EM, Bukowski JF, Tanaka Y, Band H, Bloom BR, Golan DE, Brenner MB (1995) Direct presentation of nonpeptide prenyl pyrophosphate antigens to human gamma delta T cells. Immunity 3:495

    Article  PubMed  CAS  Google Scholar 

  4. Bukowski JF, Morita CT, Brenner MB (1999) Human gamma delta T cells recognize alkylamines derived from microbes, edible plants, and tea: implications for innate immunity. Immunity 11:57

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  7. Boismenu R, Havran WL (1994) Modulation of epithelial cell growth by intraepithelial gamma delta T cells. Science 266:1253

    Article  PubMed  CAS  Google Scholar 

  8. Lahn M, Kalataradi H, Mittelstadt P, Pflum E, Vollmer M, Cady C, Mukasa A, Vella AT, Ikle D, Harbeck R, O’Brien R, Born W (1998) Early preferential stimulation of gamma delta T cells by TNF-alpha. J Immunol 160:5221

    PubMed  CAS  Google Scholar 

  9. Tough DF, Sprent J (1998) Lifespan of gamma/delta T cells. J Exp Med 187:357

    Article  PubMed  CAS  Google Scholar 

  10. Boismenu R, Feng L, Xia YY, Chang JC, Havran WL (1996) Chemokine expression by intraepithelial gamma delta T cells. Implications for the recruitment of inflammatory cells to damaged epithelia. J Immunol 157:985

    PubMed  CAS  Google Scholar 

  11. Mak TW, Ferrick DA (1998) The gammadelta T-cell bridge: linking innate and acquired immunity. Nat Med 4:764

    Article  PubMed  CAS  Google Scholar 

  12. Ferrick DA, Schrenzel MD, Mulvania T, Hsieh B, Ferlin WG, Lepper H (1995) Differential production of interferon-gamma and interleukin-4 in response to Thl and Th2-stimulating pathogens by gamma delta T cells in vivo. Nature 373:255

    Article  PubMed  CAS  Google Scholar 

  13. Wen L, Barber DF, Pao W, Wong FS, Owen MJ, Hayday A (1998) Primary gamma delta cell clones can be defined phenotypically and functionally as Thl/Th2 cells and illustrate the association of CD4 with Th2 differentiation. J Immunol 160:1965

    PubMed  CAS  Google Scholar 

  14. Kaplan DH, Shankaran V, Dighe AS, Stockert E, Aguet M, Old LJ, Schreiber RD (1998) Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci USA 95:7556

    Article  PubMed  CAS  Google Scholar 

  15. Rajan AJ, Klein JD, Brosnan CF (1998) The effect of gammadelta T cell depletion on cytokine gene expression in experimental allergic encephalomyelitis. J Immunol 160:5955

    PubMed  CAS  Google Scholar 

  16. Zuany-Amorim C, Ruffle C, Haile S, Vargaftig BB, Pereira P, Pretolani M (1998) Requirement for gammadelta T cells in allergic airway inflammation. Science 280:1265

    Article  PubMed  CAS  Google Scholar 

  17. McMenamin C, Pimm C, McKersey M, Holt PG (1994) Regulation of IgE responses in mice by antigen-specific γδ T cells. Science 265:1859

    Article  Google Scholar 

  18. McMenamin C, Mckersey M, Kühnlein P, Hünig T, Holt PG (1994) γδ T cells down-regulate primary IgE responses in rats to inhaled soluble antigens. J Immunol 154:4390

    Google Scholar 

  19. Harrison LC, Dempsey-Collier M, Kramer DR, Takahashi K (1996) Aerosol insulin induces regulatory CD8 gamma delta T cells that prevent murine insulin-dependent diabetes. J Exp Med 184: 2167

    Article  PubMed  CAS  Google Scholar 

  20. Wildner G, Hünig T, Thuran SR (1996) Orally induced, peptide-specific γ/δ TCR+ cells suppress experimental autoimmune uveitis. Eur J Immuno 126:2140

    Article  Google Scholar 

  21. Szezepamk M, Anderson L, Ushio H, Ptak W, Owen MJ, Hayday AC, Askenase PW (1996) γδ T cells from tolerized αβ T cell receptor (TCR)-deficient mice inhibit contact sensitivity-effector T cells in vivo, and their interferon-γ production in vitro. J Exp Med 184:2129

    Article  Google Scholar 

  22. Shiohara T, Moriya N, Hayakawa J, Itohara S, Ishikawa H (1996) Resistance to cutaneous graft-vs.-host disease is not induced in T cell receptor delta gene-mutant mice. J Exp Med 183:1483

    Article  PubMed  CAS  Google Scholar 

  23. Yin Z, Zhang D, Welte T, Bahtiyar G, Jung S, Liu L, Fu X, Ray A, Craft J (2000) Dominance of IL-12 over IL-4 in γδ T cell differentiation leads to default production of IFN-γ: failure to down-regulate IL-12R β2-chain expression. J Immunol 164:3056

    PubMed  CAS  Google Scholar 

  24. Ferrick DA, Schrenzel MD, Mulvania T, Hsieh B, Ferlin WG, Lepper H (1995) Differential production of interferon-γ and interleukin-4 in response to Thl - and Th2-stimulating pathogens by γδ T cells in vivo. Nature 373:255

    Article  PubMed  CAS  Google Scholar 

  25. Hsieh B, Schrenzel MD, Mulvania T, Lepper HD, DiMolfetto-Landon L, Ferrick DA (1996) In vivo cytokine production in murine listeriosis: evidence for immunoregulation by γδ+ T cells. J Immunol 156:232

    PubMed  CAS  Google Scholar 

  26. Roberts S, Smith AL, West AB, Wen L, Findly RC, Owen MJ, Hayday AC (1996) T-cell αβ+ and γδ+ deficient mice display abnormal but distinct phenotypes toward a natural, widespread infection of the intestinal epithelium. Proc Natl Acad Sci USA 3:11774

    Article  Google Scholar 

  27. Cardillo F, Falcao RP, Rossi MA, Mengél J (1993) An age-related γδ T cell suppressor activity correlates with the outcome of autoimmunity in experimental Trypanosoma cruzi infection. Eur J Immunol 23:2597

    Article  PubMed  CAS  Google Scholar 

  28. D’Souza CD, Cooper AM, Frank AA, Mazzaccaro RJ, Bloom BR, Orme IM (1997) An anti-inflammatory role for gamma delta T lymphocytes in acquired immunity to Mycobacterium tuberculosis. J Immunol 158:1217

    PubMed  CAS  Google Scholar 

  29. Vincent MS, Roessner K, Lynch D, Wilson D, Cooper SM, Tschopp J, Sigal LH, Budd RC (1996) Apoptosis of Fashigh CD4+ synovial T cells by Borrelia-reactive Fas-ligandhigh γδ T cell in Lyme arthritis. J Exp Med 184:2109

    Article  PubMed  CAS  Google Scholar 

  30. Ray A, Cohn L (1999) Th2 cells and GATA-3 in asthma: new insights into the regulation of airway inflammation. J Clin Invest 104:985

    Article  PubMed  CAS  Google Scholar 

  31. Augustin A, Kubo RT, Sim GK (1989) Resident pulmonary lymphocytes expressing the gamma/delta T-cell receptor. Nature 340:239

    Article  PubMed  CAS  Google Scholar 

  32. Spinozzi F, Agea E, Bistoni O, Forenza N, Monaco A, Falini B, Bassotti G, De Benedictis F, Grignani F, Bertotto A (1995) Local expansion of allergen-specific CD30+ Th2-type gamma delta T cells in bronchial asthma. Mol Med 1: 821

    PubMed  CAS  Google Scholar 

  33. Spinozzi F, Agea E, Bistoni O, Forenza N, Monaco A, Bassotti G, Nicoletti I, Riccardi C, Grignani F, Bertotto A (1996) Increased allergen-specific, steroid-sensitive gamma delta T cells in bronchoalveolar lavage fluid from patients with asthma. Ann Intern Med 124:223

    PubMed  CAS  Google Scholar 

  34. Chen KS, Miller KH, Hengehold D (1996) Diminution of T cells with gamma delta receptor in the peripheral blood of allergic asthmatic individuals. Clin Exp Allergy 26:295

    Article  PubMed  CAS  Google Scholar 

  35. Krejsek J, Krai B, Vokurkova D, Derner V, Touskova M, Parakova Z, Kopecky O (1998) Decreased peripheral blood gamma delta T cells in patients with bronchial asthma. Allergy 53:73

    Article  PubMed  CAS  Google Scholar 

  36. Fajac I, Roisman GL, Lacronique J, Polla BS, Dusser DJ (1997) Bronchial gamma delta T-lymphocytes and expression of heat shock proteins in mild asthma. Eur Respir J 10:633

    PubMed  CAS  Google Scholar 

  37. Korsgren M, Persson CG, Sundler F, Bjerke T, Hansson T, Chambers BJ, Hong S, Van Kaer L, Ljunggren HG, Korsgren O (1999) Natural killer cells determine development of allergen-induced eosinophilic airway inflammation in mice. J Exp Med 189:553

    Article  PubMed  CAS  Google Scholar 

  38. Lahn M, Kanehio A, Takeda K, Joetham A, Schwarze J, Kohler G, O’Brien R, Gelfand EW, Born W (1999) Negative regulation of airway responsiveness that is dependent on gammadelta T cells and independent of alphabeta T cells. Nat Med 5:1150

    Article  PubMed  CAS  Google Scholar 

  39. Clark RB, Lingenheld EG (1998) Adoptively transferred EAE in gamma delta T cell-knockout mice. J Autoimmun 11:105

    Article  PubMed  CAS  Google Scholar 

  40. Matsumoto Y, Kohyama K, Aikawa Y. Shin T, Kawazoe Y, Suzuki Y, Tan Lima N (1998) Role of natural killer cells and TCR gamma delta T cells in acute autoimmune encephalomyelitis. Eur J Immunol 28:1681

    Article  PubMed  CAS  Google Scholar 

  41. Selmaj K, Brosnan CF, Raine CS (1991) Colocalization of lymphocytes bearing gamma delta T-cell receptor and heat shock protein hsp65+ oligodendrocytes in multiple sclerosis. Proc Natl Acad Sci USA 88:6452

    Article  PubMed  CAS  Google Scholar 

  42. Birnbaum G, Kotilinek L (1997) Heat shock or stress proteins and their role as autoantigens in multiple sclerosis. Ann N Y Acad Sci 835:157

    Article  PubMed  CAS  Google Scholar 

  43. Freedman MS, Ruijs TC, Selin LK, Antel JP (1991) Peripheral blood gamma-delta T cells lyse fresh human brain-derived oligodendrocytes. Ann Neurol 30:794

    Article  PubMed  CAS  Google Scholar 

  44. Freedman MS, Buu NN, Ruijs TC, Williams K, Antel JP (1992) Differential expression of heat shock proteins by human glial cells. J Neuroimmunol 41:231

    Article  PubMed  CAS  Google Scholar 

  45. Zeine R, Pon R, Ladiwala U, Antel JP, Filion LG, Freedman MS (1998) Mechanism of gammadelta T cell-induced human oligodendrocyte cytotoxicity: relevance to multiple sclerosis. J Neuroimmunol 87:49

    Article  PubMed  CAS  Google Scholar 

  46. Rajan AJ, Gao YL, Raine CS, Brosnan CF (1996) A pathogenic role for gamma delta T cells in relapsing-remitting experimental allergic encephalomyelitis in the SJL mouse. J Immunol 157:941

    PubMed  CAS  Google Scholar 

  47. Lang FP, Schatz DA, Pollock BH, Riley WJ, Maclaren NK, Dumont-Driscoll M, Barrett DJ (1991) Increased T lymphocytes bearing the gamma-delta T cell receptor in subjects at high risk for insulin dependent diabetes. J Autoimmun 4:925

    Article  PubMed  CAS  Google Scholar 

  48. Lang FP, Pollock BH, Riley WH, Maclaren NK, Barrett DJ (1993) The temporal assocation between γδ T cells and the natural history of insulin-dependent diabetes. J Autoimmun 6:107

    Article  PubMed  CAS  Google Scholar 

  49. Gyarmati J, Szekeres-Bartho J, Fischer B, Soltesz G (1999) Fetal type lymphocytes in insulin dependent diabetes mellitus. Autoimmunity 30:63

    Article  PubMed  CAS  Google Scholar 

  50. Harrison LG, Dempsey-Collier M, Kramer DR, Takahashi K (1996) Aerosol insulin induces regulatory CDS γδ T cells that prevent murine insulin-dependent diabetes. J Exp Med 184:2167

    Article  PubMed  CAS  Google Scholar 

  51. Goldrath AW, Barber L, Chen KE, Alters SE (1995) Differences in adhesion markers, activation markers, and TcR in islet infiltrating vs. peripheral lymphocytes in the NOD mouse. J Autoimmun 8:209

    Article  PubMed  CAS  Google Scholar 

  52. Gerli R, Agea E, Bertotto A, Tognellini R, Flenghi L, Spinozzi F, Velardi A, Grignani F (1991) Analysis of T cells bearing different isotypic forms of the γ/δ T cell receptor in patients with systemic autoimmune diseases. J Rheumatol 18:1504

    PubMed  CAS  Google Scholar 

  53. Olive C, Gatenby PA, Serjeantson SW (1994) Restricted junctional diversity of T cell receptor delta gene rearrangements expressed in systemic lupus erythematosus (SLE) patients. Clin Exp Immunol 97:430

    PubMed  CAS  Google Scholar 

  54. Lunardi C, Marguerie C, Bowness P, Walport MJ, So AK (1991) Reduction in T gamma delta cell numbers and alteration in subset distribution in systemic lupus erythematosus. Clin Exp Immunol 86:203

    Article  PubMed  CAS  Google Scholar 

  55. Rajagopalan S, Zordan T, Tsokos GC, Datta SK (1990) Pathogenic anti-DNA autoantibody-inducing T helper cell lines from patients with active lupus nephritis: isolation of CD4-8− T helper cell lines that express the γδ T-cell antigen receptor. Proc Natl Acad Sci USA 87:7020

    Article  PubMed  CAS  Google Scholar 

  56. Peng SL, Madaio MP, Hayday AC, Craft J (1996) Propagation and regulation of systemic autoimmunity by gammadelta T cells. J Immunol 157:5689

    PubMed  CAS  Google Scholar 

  57. Chan O, Shlomchik MJ (1998) A new role for B cells in systemic autoimmunity: B cells promote spontaneous T cell activation in MRL-lpr/lpr mice. J Immunol 160:51

    Article  PubMed  CAS  Google Scholar 

  58. Peng SL, Madaio MP, Hughes DP, Crispe IN, Owen MJ, Wen L, Hayday AC, Craft J (1996) Murine lupus in the absence of alpha beta T cells. J Immunol 156:4041

    PubMed  CAS  Google Scholar 

  59. Ma J, Xu J, Peng Q, Zhang J, Grewal IS, Flavell RA, Craft J (1996) Autoimmune lpr/lpr mice deficient in CD40 ligand: spontaneous immunoglobulin class switching with dichotomy of autoantibody responses. J Immunol 157:417

    PubMed  CAS  Google Scholar 

  60. Peng S, Cappadona J, McNiff J, Madaio M, Owen M, Hayday A, Craft J (1998) Pathogenesis of autoimmunity in αβ T cell-deficient lupus-prone mice. Clin Exp Immunol 111:107

    Article  PubMed  CAS  Google Scholar 

  61. Peng SL, McNiff JM, Madaio MP, Ma J, Owen MJ, Flavell RA, Hayday AC, Craft J (1997) Alpha beta T cell regulation and CD40 ligand dependence in murine systemic autoimmunity. J Immunol 158:2464

    PubMed  CAS  Google Scholar 

  62. Wen L, Roberts SJ, Viney JL, Wong FS, Mallick C, Findly RC, Peng Q, Craft JE, Owen MJ, Hayday AC (1994) Immunoglobulin synthesis and generalized autoimmunity in mice congenitally deficient in αβ(+) T cells. Nature 369:654

    Article  PubMed  CAS  Google Scholar 

  63. Wen L, Pao W, Wong S, Peng Q, Craft J, Zheng B, Kelsoe G, Owen MJ, Hayday AC (1996) Germinal center formation Ig class switching and autoantibody production driven by „non αβ“ T cells. J Exp Med 183:2271

    Article  PubMed  CAS  Google Scholar 

  64. Maloy KJ, Odermatt B, Hengartner H, Zinkernagel RM (1998) Interferon gamma-producing gamma-delta T cell-dependent antibody isotype switching in the absence of germinal center formation during virus infection. Proc Natl Acad Sci USA 95:1160

    Article  PubMed  CAS  Google Scholar 

  65. Peng SL, Robert ME, Hayday AC, Craft J (1996) A tumor-suppressor function for Fas (CD95) revealed in T cell-deficient mice. J Exp Med 184:1149

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Section of Rheumatology, Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA

    Zhinan Yin & Joe Craft

  2. Section of Immunobiology, Yale School of Medicine, 610 LCI, 333 Cedar Street, Box 208031, 06520-8031, New Haven, CT, USA

    Joe Craft

Authors
  1. Zhinan Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joe Craft
    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

Yin, Z., Craft, J. γδ T cells in autoimmunity. Springer Semin Immunopathol 22, 311–320 (2000). https://doi.org/10.1007/s002810000048

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s002810000048

Keywords

Search

Navigation