Skip to main content
NCBI home page
Mediators of Inflammation logoLink to Mediators of Inflammation
. 1999;8(6):305–312. doi: 10.1080/09629359990315

Circulating TCR gammadelta cells in the patients with systemic lupus erythematosus.

E Robak 1, J Z Błoński 1, J Bartkowiak 1, H Niewiadomska 1, A Sysa-Jedrzejowska 1, T Robak 1
PMCID: PMC1781811  PMID: 10815619

Abstract

Systemic lupus erythematosus (SLE) is a disorder with a wide range of immunological abnormalities. The results of the studies undertaken in the last decade indicated that SLE pathogenesis was mainly connected with the breakdown of the activation control of B and T cells, generating humoral or cell-mediated responses against several self-antigens of affected cells. The last studies demonstrate that the role of gammadelta T lymphocytes in autoimmune diseases can be especially important. Flow cytometry techniques were used to investigate the number and percentage of TCR gammadelta T cells and their most frequent subtypes in peripheral blood of 32 patients with SLE and 16 healthy volunteers. We also correlated TCR gammadelta cells number with the level of T CD3+, T CD4+, T CD8+, and NK (CD16) cells (cytometric measurements) and SLE activity (on the basis of clinical investigations). Our studies were preliminary attempts to evaluate the role of that minor T cell subpopulation in SLE. Absolute numbers of cells expressing gammadelta TCR in most SLE blood specimens were significantly lower than in the control group (P<0.006). However, since the level of total T cell population was also decreased in the case of SLE, the mean values of the percentage gammadelta T cells of pan T lymphocytes were almost the same in both analysed populations (7.1% vs 6.3%, respectively). In contrast to Vdelta2+ and Vgamma9+ subtypes of pan gammadelta T cells, Vdelta3+ T cells number was higher in SLE patients (20 x 10 cells/microl) than in healthy control group (2 x 2 cells/microl) (P=0.001). However, we found no differences between the numbers of pan gammadelta T lymphocytes and studied their subtypes in the patients with active and inactive disease. These cell subpopulations were doubled in the treated patients with immunosuppressive agents in comparison with untreated ones; however, data were not statistically significant. Our study indicated that Vdelta3+ subtype of gammadelta T cells seems to be involved in SLE pathogenesis; however, we accept the idea that the autoimmunity does not develop from a single abnormality, but rather from a number of different events.

Full Text

The Full Text of this article is available as a PDF (218.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bluestone J. A., Khattri R., Sciammas R., Sperling A. I. TCR gamma delta cells: a specialized T-cell subset in the immune system. Annu Rev Cell Dev Biol. 1995;11:307–353. doi: 10.1146/annurev.cb.11.110195.001515. [DOI] [PubMed] [Google Scholar]
  2. Bordessoule D., Gaulard P., Mason D. Y. Preferential localisation of human lymphocytes bearing gamma delta T cell receptors to the red pulp of the spleen. J Clin Pathol. 1990 Jun;43(6):461–464. doi: 10.1136/jcp.43.6.461. [DOI] [PMC free article] [PubMed] [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., Krangel M. S. Identification of a putative second T-cell receptor. Nature. 1986 Jul 10;322(6075):145–149. doi: 10.1038/322145a0. [DOI] [PubMed] [Google Scholar]
  4. Davis M. M., Bjorkman P. J. T-cell antigen receptor genes and T-cell recognition. Nature. 1988 Aug 4;334(6181):395–402. doi: 10.1038/334395a0. [DOI] [PubMed] [Google Scholar]
  5. Gerli R., Agea E., Bertotto A., Tognellini R., Flenghi L., Spinozzi F., Velardi A., Grignani F. Analysis of T cells bearing different isotypic forms of the gamma/delta T cell receptor in patients with systemic autoimmune diseases. J Rheumatol. 1991 Oct;18(10):1504–1510. [PubMed] [Google Scholar]
  6. Giacomelli R., Matucci-Cerinic M., Cipriani P., Ghersetich I., Lattanzio R., Pavan A., Pignone A., Cagnoni M. L., Lotti T., Tonietti G. Circulating Vdelta1+ T cells are activated and accumulate in the skin of systemic sclerosis patients. Arthritis Rheum. 1998 Feb;41(2):327–334. doi: 10.1002/1529-0131(199802)41:2<327::AID-ART17>3.0.CO;2-S. [DOI] [PubMed] [Google Scholar]
  7. Hayday A. Autoimmunity. Is antigen-specific suppression now unsuppressed? Curr Biol. 1995 Jan 1;5(1):47–50. doi: 10.1016/s0960-9822(95)00015-7. [DOI] [PubMed] [Google Scholar]
  8. Hayday A., Geng L. Gamma delta cells regulate autoimmunity. Curr Opin Immunol. 1997 Dec;9(6):884–889. doi: 10.1016/s0952-7915(97)80193-8. [DOI] [PubMed] [Google Scholar]
  9. Hohlfeld R., Engel A. G., Ii K., Harper M. C. Polymyositis mediated by T lymphocytes that express the gamma/delta receptor. N Engl J Med. 1991 Mar 28;324(13):877–881. doi: 10.1056/NEJM199103283241303. [DOI] [PubMed] [Google Scholar]
  10. Holoshitz J., Koning F., Coligan J. E., De Bruyn J., Strober S. Isolation of CD4- CD8- mycobacteria-reactive T lymphocyte clones from rheumatoid arthritis synovial fluid. Nature. 1989 May 18;339(6221):226–229. doi: 10.1038/339226a0. [DOI] [PubMed] [Google Scholar]
  11. Ishida H., Kumagai S., Umehara H., Sano H., Tagaya Y., Yodoi J., Imura H. Impaired expression of high affinity interleukin 2 receptor on activated lymphocytes from patients with systemic lupus erythematosus. J Immunol. 1987 Aug 15;139(4):1070–1074. [PubMed] [Google Scholar]
  12. Jacobs M. R., Haynes B. F. Increase in TCR gamma delta T lymphocytes in synovia from rheumatoid arthritis patients with active synovitis. J Clin Immunol. 1992 Mar;12(2):130–138. doi: 10.1007/BF00918143. [DOI] [PubMed] [Google Scholar]
  13. Jarry A., Cerf-Bensussan N., Brousse N., Selz F., Guy-Grand D. Subsets of CD3+ (T cell receptor alpha/beta or gamma/delta) and CD3- lymphocytes isolated from normal human gut epithelium display phenotypical features different from their counterparts in peripheral blood. Eur J Immunol. 1990 May;20(5):1097–1103. doi: 10.1002/eji.1830200523. [DOI] [PubMed] [Google Scholar]
  14. Kaufmann S. H. Heat shock proteins and the immune response. Immunol Today. 1990 Apr;11(4):129–136. doi: 10.1016/0167-5699(90)90050-j. [DOI] [PubMed] [Google Scholar]
  15. Keystone E. C., Rittershaus C., Wood N., Snow K. M., Flatow J., Purvis J. C., Poplonski L., Kung P. C. Elevation of a gamma delta T cell subset in peripheral blood and synovial fluid of patients with rheumatoid arthritis. Clin Exp Immunol. 1991 Apr;84(1):78–82. [PMC free article] [PubMed] [Google Scholar]
  16. Lew A. M., Pardoll D. M., Maloy W. L., Fowlkes B. J., Kruisbeek A., Cheng S. F., Germain R. N., Bluestone J. A., Schwartz R. H., Coligan J. E. Characterization of T cell receptor gamma chain expression in a subset of murine thymocytes. Science. 1986 Dec 12;234(4782):1401–1405. doi: 10.1126/science.3787252. [DOI] [PubMed] [Google Scholar]
  17. Liang M. H., Socher S. A., Larson M. G., Schur P. H. Reliability and validity of six systems for the clinical assessment of disease activity in systemic lupus erythematosus. Arthritis Rheum. 1989 Sep;32(9):1107–1118. doi: 10.1002/anr.1780320909. [DOI] [PubMed] [Google Scholar]
  18. Linker-Israeli M., Deans R. J., Wallace D. J., Prehn J., Ozeri-Chen T., Klinenberg J. R. Elevated levels of endogenous IL-6 in systemic lupus erythematosus. A putative role in pathogenesis. J Immunol. 1991 Jul 1;147(1):117–123. [PubMed] [Google Scholar]
  19. Linker-Israeli M., Quismorio F. P., Jr, Horwitz D. A. CD8+ lymphocytes from patients with systemic lupus erythematosus sustain, rather than suppress, spontaneous polyclonal IgG production and synergize with CD4+ cells to support autoantibody synthesis. Arthritis Rheum. 1990 Aug;33(8):1216–1225. doi: 10.1002/art.1780330823. [DOI] [PubMed] [Google Scholar]
  20. Martins E. B., Graham A. K., Chapman R. W., Fleming K. A. Elevation of gamma delta T lymphocytes in peripheral blood and livers of patients with primary sclerosing cholangitis and other autoimmune liver diseases. Hepatology. 1996 May;23(5):988–993. doi: 10.1002/hep.510230508. [DOI] [PubMed] [Google Scholar]
  21. Mukasa A., Hiromatsu K., Matsuzaki G., O'Brien R., Born W., Nomoto K. Bacterial infection of the testis leading to autoaggressive immunity triggers apparently opposed responses of alpha beta and gamma delta T cells. J Immunol. 1995 Aug 15;155(4):2047–2056. [PubMed] [Google Scholar]
  22. Olive C., Gatenby P. A., Serjeantson S. W. Restricted junctional diversity of T cell receptor delta gene rearrangements expressed in systemic lupus erythematosus (SLE) patients. Clin Exp Immunol. 1994 Sep;97(3):430–438. doi: 10.1111/j.1365-2249.1994.tb06106.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Peng S. L., Madaio M. P., Hayday A. C., Craft J. Propagation and regulation of systemic autoimmunity by gammadelta T cells. J Immunol. 1996 Dec 15;157(12):5689–5698. [PubMed] [Google Scholar]
  24. Peng S. L., Madaio M. P., Hughes D. P., Crispe I. N., Owen M. J., Wen L., Hayday A. C., Craft J. Murine lupus in the absence of alpha beta T cells. J Immunol. 1996 May 15;156(10):4041–4049. [PubMed] [Google Scholar]
  25. Robak E., Sysa-Jedrzejowska A., Stepień H., Robak T. Circulating interleukin-6 type cytokines in patients with systemic lupus erythematosus. Eur Cytokine Netw. 1997 Sep;8(3):281–286. [PubMed] [Google Scholar]
  26. Roura-Mir I. C., Alcalde L., Vargas F., Tolosa E., Obiols G., Foz M., Jaraquemada D., Pujol-Borrell R. Gamma delta lymphocytes in endocrine autoimmunity: evidence of expansion in Graves' disease but not in type 1 diabetes. Clin Exp Immunol. 1993 May;92(2):288–295. doi: 10.1111/j.1365-2249.1993.tb03394.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sakane T., Steinberg A. D., Green I. Studies of immune functions of patients with systemic lupus erythematosus. I. Dysfunction of suppressor T-cell activity related to impaired generation of, rather than response to, suppressor cells. Arthritis Rheum. 1978 Jul-Aug;21(6):657–664. doi: 10.1002/art.1780210608. [DOI] [PubMed] [Google Scholar]
  28. Selmaj K., Brosnan C. F., Raine C. S. Colocalization of lymphocytes bearing gamma delta T-cell receptor and heat shock protein hsp65+ oligodendrocytes in multiple sclerosis. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6452–6456. doi: 10.1073/pnas.88.15.6452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Spinozzi F., Agea E., Bistoni O., Travetti A., Migliorati G., Moraca R., Nicoletti I., Riccardi C., Paoletti F. P., Vaccaro R. T lymphocytes bearing the gamma delta T cell receptor are susceptible to steroid-induced programmed cell death. Scand J Immunol. 1995 May;41(5):504–508. doi: 10.1111/j.1365-3083.1995.tb03599.x. [DOI] [PubMed] [Google Scholar]
  30. Steinberg A. D., Klinman D. M. Pathogenesis of systemic lupus erythematosus. Rheum Dis Clin North Am. 1988 Apr;14(1):25–41. [PubMed] [Google Scholar]
  31. Stinissen P., Vandevyver C., Medaer R., Vandegaer L., Nies J., Tuyls L., Hafler D. A., Raus J., Zhang J. Increased frequency of gamma delta T cells in cerebrospinal fluid and peripheral blood of patients with multiple sclerosis. Reactivity, cytotoxicity, and T cell receptor V gene rearrangements. J Immunol. 1995 May 1;154(9):4883–4894. [PubMed] [Google Scholar]
  32. Swaak A. J., Nossent J. C., Smeenk R. J. Systemic lupus erythematosus. Int J Clin Lab Res. 1992;22(4):190–195. doi: 10.1007/BF02591422. [DOI] [PubMed] [Google Scholar]
  33. Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N., Winchester R. J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. doi: 10.1002/art.1780251101. [DOI] [PubMed] [Google Scholar]
  34. Tsokos G. C., Magrath I. T., Balow J. E. Epstein-Barr virus induces normal B cell responses but defective suppressor T cell responses in patients with systemic lupus erythematosus. J Immunol. 1983 Oct;131(4):1797–1801. [PubMed] [Google Scholar]
  35. Volc-Platzer B., Anegg B., Milota S., Pickl W., Fischer G. Accumulation of gamma delta T cells in chronic cutaneous lupus erythematosus. J Invest Dermatol. 1993 Jan;100(1):84S–91S. doi: 10.1111/1523-1747.ep12356084. [DOI] [PubMed] [Google Scholar]
  36. Yurovsky V. V., Sutton P. A., Schulze D. H., Wigley F. M., Wise R. A., Howard R. F., White B. Expansion of selected V delta 1+ gamma delta T cells in systemic sclerosis patients. J Immunol. 1994 Jul 15;153(2):881–891. [PubMed] [Google Scholar]
  37. al-Janadi M., al-Balla S., al-Dalaan A., Raziuddin S. Cytokine production by helper T cell populations from the synovial fluid and blood in patients with rheumatoid arthritis. J Rheumatol. 1993 Oct;20(10):1647–1653. [PubMed] [Google Scholar]

Articles from Mediators of Inflammation are provided here courtesy of Wiley

RESOURCES