Skip to main content
SpringerLink
Log in

The role ofγδ T cells in the normal and disordered immune system

  • Review
  • Published:
Klinische Wochenschrift Aims and scope Submit manuscript

Summary

A small population of T cells does not express the conventional T cell receptor characterized by theα andβ polypeptide chains (TCRαβ) but instead, two polypeptides termedγ andδ (TCRγδ). This alternative receptor is able to recognize antigen. It appears early in T cell ontogeny, but its role in the thymus prior to the availability of TCRαβ remains unclear. In selected sites such as skin or gut TCRγδ predominates in mice which might suggest a role ofγδ T cells in the first line of defense against infection,γδ T cells secrete lymphokines and display cytotoxic activity. However, their activation requirements may differ from what is known forαβ T cells since MHC-nonrestricted and also CD4 and CD8 negativeγδ T cells have been described. Preferential activation by mycobacterial antigens possibly indicates a special repertoire of theγδ T cells. In various diseases slightly increased numbers ofγδ T cells were found, but these preliminary studies have not yet provided evidence for a major pathogenetic role ofγδ T cells.

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

Abbreviations

C:

constant region (immunoglobulin or TCR gene segment)

CD4:

cluster of differentiation 4 (mainly on helper cells)

CD8:

cluster of differentiation 8 (mainly on cytotoxic cells)

D:

diversity region (immunoglobulin or TCR gene segment)

DNA:

desoxyribonucleic acid

IL2:

interleukin 2

J:

joining region (immunoglobulin or TCR gene segment)

kD:

kiloDalton

MHC:

major histocompatibility complex

NK:

natural killer (cells)

RA:

rheumatoid arthritis

TCR:

T cell receptor

V:

variable region (immunoglobulin or TCR gene segment)

References

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

    Google Scholar 

  2. Augustin A, Kubo RT, Sim G (1989) Resident pulmonary lymphocytes expressing theγ/δ T cell receptor. Nature 340:239–241

    Google Scholar 

  3. Bluestone J, Pardoll D, Sharrow S, Fowlkes B (1987) Characterization of murine thymocytes with CD3-associated T cell receptor structures. Nature 326:82–84

    Google Scholar 

  4. Bonneville M, Janeway CA, Ito K, Haser W, Ishida I, Nakanishi N, et al. (1988) Intestinal intraepithelial lymphocytes are a distinct set ofγδ T cells. Nature 336:479–481

    Google Scholar 

  5. Bosnes V, Halvorsen R, Skaftadottir I, Gaudernack G, Thorsby E (1989) Specificity ofγδ receptor-bearing cytotoxic T lymphocytes isolated from human peripheral blood. Scand J Immunol 29:723–731

    Google Scholar 

  6. Brandtzaeg P, Halstensen TS, Scott H, Sollid LM, Valnes K (1989) Epithelial homing ofγδ T cells? Nature 341:113

    Google Scholar 

  7. Brennan FM, Londei M, Jackson AM, Hercend T, Brenner MB, Maini RN, et al. (1988) T cells expressingγδ chain receptors in rheumatoid arthritis. J Autoimmunity 1:319–326

    Google Scholar 

  8. Brennan F, Plater-Zyberk C, Maini RN, Feldmann M (1989) Coordinate expansion of “fet al type” lymphocytes (TCRγδ+ T and CD5+ B) in rheumatoid arthritis and primary Sjögren's syndrome. Clin Exp Immunol 77:175–178

    Google Scholar 

  9. Brenner MB, McLean J, Scheft H, Riberdy J, Aug S, Seidman JG, et al. (1987) Two forms of the T cell receptorγ protein found on peripheral blood cytotoxic T-lymphocytes. Nature 325:689–694

    Google Scholar 

  10. Bucy RP (1989) Epithelial homing ofγδ T cells? Nature 341:113–114

    Google Scholar 

  11. Bucy RP, Chen CH, Cihak J, Lösch U, Cooper MD (1988) Avian T cells expressingγδ receptors localize in the splenic sinusoids and the intestinal epithelium. J Immunol 141:2200–2205

    Google Scholar 

  12. Bucy RP, Chen CH, Cooper MD (1989) Tissue localization and CD8 accessory molecule expression of Tγδ cells in humans. J Immunol 142:3045–3049

    Google Scholar 

  13. Campana D, Janossy G, Coustan-Smith E, Amlot PL, Tian W, Ip S, et al. (1989) The expression of T cell receptor-associated proteins during T cell ontogeny in man. J Immunol 142:57–66

    Google Scholar 

  14. Ciccone E, Ferrini S, Bottino C, Viale O, Prigione I, Pantaleo G, et al. (1988) A monoclonal antibody specific for a common determinant of the human T cell receptorγ directly activates CD3+ WT31-lymphocytes to express their functional program. J Exp Med 168:1–11

    Google Scholar 

  15. Ciccone E, Viale O, Bottino C, Pende D, Migone N, Casorati G, et al. (1988) Antigen recognition by human T cell receptorγ-positive lymphocytes. J Exp Med 167:1517–1522

    Google Scholar 

  16. Cron R, Koning F, Maloy W, Pardoll D, Coligan J, Bluestone J (1988) Peripheral murine CD3+, CD4−, CD8− T lymphocytes express novel T cell receptorγδ structures. J Immunol 141:1074–1082

    Google Scholar 

  17. Davis MM, Bjorkman PJ (1988) T cell antigen receptor genes and T cell recognition. Nature 334:395–402

    Google Scholar 

  18. DeMaria A, Malnati M, Moretta A, Pende D, Bottino C, Casorati G, et al. (1987) CD3+4 −WT31−(T cell receptorγ+) cells and other unusual phenotypes are frequently detected among spontaneously interleukin 2-responsive T lymphocytes present in the joint fluid in juvenile rheumatoid arthritis. Eur J Immunol 17:1815–1819

    Google Scholar 

  19. DeVillartay J, Hocket RD, Coran D, Korsmeyer S, Cohen DI (1988) Deletion of the human T cell receptorδ-gene by a site-specific recombination. Nature 335:170–174

    Google Scholar 

  20. Ferrini S, Zarcone D, Viale M, Cerruti G, Millo R, Moretta A, et al. (1989) Morphologic and functional characterization of human peripheral blood T cells expressing the T cell receptorγ/δ. Eur J Immunol 19:1183–1188

    Google Scholar 

  21. Fortune F, Kington J, Courteau M, Walker J, Williams G, Lehnert T (1989) Up-regulation of TCR-γδ expression in human T cells after immunization and in autoimmune diseases. Abstract. British Society for Immunology, Autumn Meeting, London 1–3 November 1989, 41

  22. Goodman T, Lefrancois L (1988) Expression of theγ-δ T cell receptor on intestinal CD8+ intraepithelial lymphocytes. Nature 333:855–858

    Google Scholar 

  23. Groh V, Porcelli S, Fabbi M, Lanier L, Picker LJ, Anderson T, et al. (1989) Human lymphocytes bearing T cell receptorγ/δ are phenotypically diverse and evenly distributed in the lymphoid system. J Exp Med 169:1277–1294

    Google Scholar 

  24. Haregwoin A, Soman G, Hom RC, Finberg RW (1989) Humanγδ+ T cells respond to mycobacterial heat-shock protein. Nature 340:309–312

    Google Scholar 

  25. Hochstenbach F, Brenner MB (1989) T cell receptorδ-chain can substitute forα to form aβδ heterodimer. Nature 340:562–565

    Google Scholar 

  26. Hockett RD, Villartay J-P, Pollock K, Poplack DG, Cohen DI, Korsmeyer SJ (1988) Human T cell antigen receptor (TCR)δ-chain locus and elements responsible for its deletion are within theα-chain locus. Proc Natl Acad Sci USA 85:9694–9698

    Google Scholar 

  27. Holoshitz J, Matitiau A, Cohen IR (1984) Arthritis induced in rats by cloned T lymphocytes responsive to mycobacteria but not to collagen type II. J Clin Invest 73:211–215

    Google Scholar 

  28. Holoshitz J, Koning F, Coligan JE, DeBruyn J, Strober S (1989) Isolation of CD4−CD8− mycobacteria-reactive T lymphocyte clones from rheumatoid arthritis synovial fluid. Nature 339:226–229

    Google Scholar 

  29. Janeway CA, Jones B, Hayday A (1988) Specificity and function of T cells bearingγδ receptors. Immunol Today 9:73–76

    Google Scholar 

  30. Janis EM, Kaufmann SHE, Schwartz RH, Pardoll DM (1989) Activation ofγδ T cells in the primary immune response to mycobacterium tuberculosis. Science 244:713–716

    Google Scholar 

  31. Kozbor D, Trinchieri G, Monos DS, Isobe M, Russo G, Haney JA, et al. (1989) Human TCR-γ/+/δ+, CD8+ T lymphocytes recognize tetanus toxoid in an MHC-restricted fashion. J Exp Med 169:1847–1851

    Google Scholar 

  32. Krangel MS, Band H, Hata S, McLean J, Brenner MB (1987) Structurally divergent human T cell receptorγ-proteins encoded by distinct Cγ genes. Science 237:64–67

    Google Scholar 

  33. Kyes S, Carew E, Carding SR, Janeway C, Hayday A (1989) Diversity in T cell receptorγ gene usage in intestinal epithelium. Proc Natl Acad Sci USA 86:5527–5531

    Google Scholar 

  34. Lefranc M-P, Chuchana P, Dariavach P, Nguyen C, Huck S, Brockly F, Jordan B, Lefranc G (1989) Molecular mapping of the human T cell receptor gamma (TCR) genes and linkage of the variable and constant regions. Eur J Immunol 19:989–994

    Google Scholar 

  35. Lefrancois L, Goodman T (1989) In vivo modulation of cytolytic activity and Thy-1 expression in TCR-γδ+ intraepithelial lymphocytes. Science 243:1716–1718

    Google Scholar 

  36. Littman DR, Newton M, Crommie D, Ang SL, Seidman JG, Gettner SN, et al. (1987) Characterization of an expressed CD3-associated Ti -chain reveals C-γ domain polymorphism. Nature 326:85–88

    Google Scholar 

  37. Loh EY, Cwirla S, Serafini AT, Phillips JH, Lanier LL (1988) Human T cell-receptorδ chain: genomic organization, diversity, and expression in populations of cells. Proc Natl Acad Sci USA 97:9714–9718

    Google Scholar 

  38. MacKay CR, Beya M, Matzinger P (1989)γ/δ T cells express a unique surface molecule appearing late during thymic development. Eur J Immunol 19:1477–1483

    Google Scholar 

  39. Maeda K, Nakanishi N, Rogers BL, Haser WG, Shitara K, Yoshida H, et al. (1987) Expression of the T cell receptorγ-chain gene products on the surface of peripheral T cells and T cell blasts generated by allogeneic mixed lymphocyte reaction. Proc Natl Acad Sci USA 84:6536–6540

    Google Scholar 

  40. Modlin RL, Pirmez C, Hofman FM, Torigian V, Uyemura K, Rea TH, et al. (1989) Lymphocytes bearing antigen-specificγδ T cell receptors accumulate in human infectious disease lesions. Nature 339:544–548

    Google Scholar 

  41. Moretta L, Ciccone E, Mingari MC, Bottino C, Ferrini S, Tambussi G, et al. (1989) T lymphocytes expressingγ/δ T cell antigen receptor. Clin Immunol Immunopathol 50:117–123

    Google Scholar 

  42. Nakanishi N, Maeda K, Ito K, Heller M, Tonegawa S (1987) Tγ protein is expressed on murine fetal thymocytes as a disulfide-linked heterodimer. Nature 325:720–723

    Google Scholar 

  43. O'Brien R, Happ MP, Dallas A, Palmer E, Kubo R, Born WK (1989) Stimulation of a major subset of lymphocytes expressing the T cell receptorγδ by an antigen derived from mycobacterium tuberculosis. Cell 57:667–674

    Google Scholar 

  44. Pardoll DM, Fowlkes BJ, Bluestone JA, Kruisbeek A, Maloy WL, Coligan JE, et al. (1987) Differential expression of two distinct T cell receptors during thymocyte development. Nature 326:79–81

    Google Scholar 

  45. Pardoll DM, Folwkes BJ, Lew AM, Maloy WL, Weston M, Bluestone JA, et al. (1988) Thymus-dependent and thymus-independent developmental pathways for peripheral T cell receptor-γδ-bearing lymphocytes. J Immunol 140:4091–4096

    Google Scholar 

  46. Quayle AJ, Kjeldsen-Krag J, Førre Ø, Kalveness C, Natvig J (1989) The distribution of Tγδ cells in rheumatoid arthritis and juvenile rheumatoid arthritis. Abstract. British Society for Immunology, Autumn Meeting, London 1–3 November 1989, 44

  47. Raulet DA (1989) The structure, function, and molecular genetics of theγδ T cell receptor. Ann Rev Immunol 7:175–207

    Google Scholar 

  48. Smith M, Bröker B, Moretta L, Ciccone E, Grossi C, Edwards J, et al. (1990)γδ T cells in patients with rheumatoid arthritis. Scand J Immunol (submitted)

  49. Sowder JT, Chen CL, Ager LL, Chan MM, Cooper MD (1988) A large subpopulation of avian T cells express a homologue of the mammalian Tγδ receptor. J Exp Med 167:315–322

    Google Scholar 

  50. Spencer J, Isaacson PG, Diss TC, MacDonald TT (1989) Expression of disulfide-linked and non-disulfide-linked forms of the T cell receptorγ/δ heterodimer in human intestinal intraepithelial lymphocytes. Eur J Immunol 19:1335–1338

    Google Scholar 

  51. Stingl G, Koning F, Yamada H, Yokoyama WM, Tschachler E, Bluestone J, et al. (1987) Thy-1 + dendritic epidermal cells express T3 antigen and the T cell receptorγ chain. Proc Natl Acad Sci USA 84:4586–4590

    Google Scholar 

  52. Strominger J (1989) Theγ/δ T cell receptor and class 1b MHC-related proteins: enigmatic molecules of recognition. Cell 57:895–898

    Google Scholar 

  53. Sturm E, Braakman E, Bontrop RE, Chuchana P, Van de Griend R, Koning F, et al. (1989) Coordinated V and Vδ gene segment rearrangements in human T cell receptorγ/δ+ lymphocytes. Eur J Immunol 19:1261–1265

    Google Scholar 

  54. Takeshita S, Toda M, Yamagishi H (1989) Excision products of the T cell receptor gene support a progressive rearrangement model of theα/δ locus. EMBO 8:3261–3270

    Google Scholar 

  55. Triebel F, Hercend T (1989) Subpopulations of human peripheral gamma delta lymphocytes. Immunol Today 10:186–188

    Google Scholar 

  56. van Dongen JJM, Comans-Bitter WM, Friedrich W, Neijens HJ, Belohradsky BH, Kohn T, et al. (1989) Expression of the classical T cell receptor (TCR-αβ) and the alternative T cell receptor (TCR-γδ) in athymic children and normal children. Abstract. 7th International Congress of Immunology, Berlin 30 July–5 August 1989, 188

  57. van Eden W, Thole JER, van der Zee K, Noordzij A, van Embden JDA, Hensen EJ, Cohen JR (1988) Cloning of the mycobacterial epitope recognized by T lymphocytes in adjuvant arthritis. Nature 331:171–173

    Google Scholar 

  58. Vidović D, Roglić M, McCune K, Guerder S, MacKay C, Demić Z (1989) Qa-1 restricted recognition of foreign antigen by aγδ T cell hybridoma. Nature 340:646–650

    Google Scholar 

  59. Vroom TM, Bos JD, Borst J (1989) Epithelial homing ofγδ T cells? Nature 341:114

    Google Scholar 

  60. Winoto A, Baltimore D (1989) Separate lineages of T cells expressing theαβ andγδ receptors. Nature 338:430–432

    Google Scholar 

  61. Yachie A, Ueno Y, Takano N, Miyawaki T, Taniguchi N (1989) Developmental changes of double-negative (CD3−4−8−) T cells in human peripheral blood. Clin Exp Immunol 76:258–261

    Google Scholar 

  62. Yoshikai Y, Reis MD, Mak TW (1986) Athymic mice express a high level ofγ-andβ-chain T cell receptor messages. Nature 324:482–485

    Google Scholar 

  63. Yoshino S, Schlipköter E, Kinne R, Hünig T, Emmrich F (1990) Suppression and prevention of adjuvant arthritis in rats by a monoclonal antibody to theαβ T cell receptor. J Exp Immunol (submitted)

Download references

Author information

Authors and Affiliations

  1. MPG Gruppe Rheumatologie/Immunologie, Max-Planck-Gesellschaft, Erlangen

    B. Bröker & F. Emmrich

  2. Department for Immunology, University College and Middlesex School of Medicine, London

    P. M. Lydyard

Authors
  1. B. Bröker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. M. Lydyard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. Emmrich
    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

Bröker, B., Lydyard, P.M. & Emmrich, F. The role ofγδ T cells in the normal and disordered immune system. Klin Wochenschr 68, 489–495 (1990). https://doi.org/10.1007/BF01648239

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01648239

Key words

Search

Navigation