Abstract
Human Tgammadelta lymphocytes constitute from 1 to 15% of all peripheral blood lymphocytes. Recent work has demonstrated that this population plays a major role in the pathogenesis of infectious and immune diseases. Increased numbers of gammadelta T cells have been found in affected skin from systemic sclerosis and chronic cutaneous lupus erythematosus patients. In our study, we have determined the numbers of Tgammadelta lymphocytes and their subpopulations in peripheral blood from 29 patients with systemic lupus erythematosus (SLE) and in 19 healthy volunteers using flow cytometry and specific monoclonal antibodies. The same cells in uninvolved skin from SLE patients and human controls using immunohistochemical analysis were estimated. T-Cell receptor (TCR) delta chain gene rearrangement was identified with primers for Vdelta1, Vdelta2 and Vdelta3 by the polymerase chain reaction. Statistical analysis showed a significantly decreased number of gammadelta T cells in SLE patients (26.4+/-16.9/microl) compared with the control group (55.3+/-20.6/microl (p < 0.001). The number of Vdelta2 TCR+ and Vgamma9 TCR+ subpopulations was also lower in SLE patients than in healthy persons. No statistical correlation between disease activity and the number of gammadelta T cells was demonstrated. The percentage of Tgammadelta lymphocytes in clinically normal skin from SLE patients was twice (22.0+/-9.4%) that found in the skin from healthy persons (11.1+/-5.5%) (p < 0.002). Higher percentages of the Vdelta2 TCR+ and Vgamma9 TCR+ subpopulation of lymphocytes were found in the skin from SLE patients. We have also found positive correlation between the percentage of Tgammadelta lymphocytes in skin and the activity of SLE (r=0.594, p < 0.001), and between subpopulation Vdelta3 TCR+ and disease activity (r=0.659, p< 0.001). In conclusion, the results of our studies demonstrate that, in patients with SLE, accumulation of Tgammadelta lymphocytes can be seen in clinically normal skin, and the percentage of these cells correlates with the activity of the disease.
Full Text
The Full Text of this article is available as a PDF (279.0 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bakke A. C., Kirkland P. A., Kitridou R. C., Quismorio F. P., Jr, Rea T., Ehresmann G. R., Horwitz D. A. T lymphocyte subsets in systemic lupus erythematosus. Correlations with corticosteroid therapy and disease activity. Arthritis Rheum. 1983 Jun;26(6):745–750. doi: 10.1002/art.1780260607. [DOI] [PubMed] [Google Scholar]
- 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]
- Boismenu R., Havran W. L. An innate view of gamma delta T cells. Curr Opin Immunol. 1997 Feb;9(1):57–63. doi: 10.1016/s0952-7915(97)80159-8. [DOI] [PubMed] [Google Scholar]
- 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]
- Borst J., van de Griend R. J., van Oostveen J. W., Ang S. L., Melief C. J., Seidman J. G., Bolhuis R. L. A T-cell receptor gamma/CD3 complex found on cloned functional lymphocytes. Nature. 1987 Feb 19;325(6106):683–688. doi: 10.1038/325683a0. [DOI] [PubMed] [Google Scholar]
- Brenner M. B., McLean J., Scheft H., Riberdy J., Ang S. L., Seidman J. G., Devlin P., Krangel M. S. Two forms of the T-cell receptor gamma protein found on peripheral blood cytotoxic T lymphocytes. Nature. 1987 Feb 19;325(6106):689–694. doi: 10.1038/325689a0. [DOI] [PubMed] [Google Scholar]
- Converso M., Bertero M. T., Vallario A., Caligaris-Cappio F. Analysis of T-cell clones in systemic lupus erythematosus. Haematologica. 2000 Feb;85(2):118–123. [PubMed] [Google Scholar]
- Cronstein B. N., Weissmann G. The adhesion molecules of inflammation. Arthritis Rheum. 1993 Feb;36(2):147–157. doi: 10.1002/art.1780360204. [DOI] [PubMed] [Google Scholar]
- Davodeau F., Peyrat M. A., Houde I., Hallet M. M., De Libero G., Vié H., Bonneville M. Surface expression of two distinct functional antigen receptors on human gamma delta T cells. Science. 1993 Jun 18;260(5115):1800–1802. doi: 10.1126/science.8390096. [DOI] [PubMed] [Google Scholar]
- Delves P. J., Roitt I. M. The immune system. First of two parts. N Engl J Med. 2000 Jul 6;343(1):37–49. doi: 10.1056/NEJM200007063430107. [DOI] [PubMed] [Google Scholar]
- Fujita M., Miyachi Y., Nakata K., Imamura S. Gamma delta T-cell receptor-positive cells in human skin. I. Incidence and V-region gene expression in granulomatous skin lesions. J Am Acad Dermatol. 1993 Jan;28(1):46–50. doi: 10.1016/0190-9622(93)70007-g. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Hettinger K., Fischer S., Panzer S., Panzer-Grümayer E. R. Multiplex PCR for TCR delta rearrangements: a rapid and specific approach for the detection and identification of immature and mature rearrangements in ALL. Br J Haematol. 1998 Sep;102(4):1050–1054. doi: 10.1046/j.1365-2141.1998.00879.x. [DOI] [PubMed] [Google Scholar]
- 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]
- Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Krangel M. S., Band H., Hata S., McLean J., Brenner M. B. Structurally divergent human T cell receptor gamma proteins encoded by distinct C gamma genes. Science. 1987 Jul 3;237(4810):64–67. doi: 10.1126/science.2955517. [DOI] [PubMed] [Google Scholar]
- Lanier L. L., Federspiel N. A., Ruitenberg J. J., Phillips J. H., Allison J. P., Littman D., Weiss A. The T cell antigen receptor complex expressed on normal peripheral blood CD4-, CD8- T lymphocytes. A CD3-associated disulfide-linked gamma chain heterodimer. J Exp Med. 1987 Apr 1;165(4):1076–1094. doi: 10.1084/jem.165.4.1076. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lauzurica P., Krangel M. S. Temporal and lineage-specific control of T cell receptor alpha/delta gene rearrangement by T cell receptor alpha and delta enhancers. J Exp Med. 1994 Jun 1;179(6):1913–1921. doi: 10.1084/jem.179.6.1913. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lefranc M. P., Rabbitts T. H. Genetic organization of the human T-cell receptor gamma and delta loci. Res Immunol. 1990 Sep;141(7):565–577. doi: 10.1016/0923-2494(90)90058-7. [DOI] [PubMed] [Google Scholar]
- 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]
- Lunardi C., Marguerie C., Bowness P., Walport M. J., So A. K. Reduction in T gamma delta cell numbers and alteration in subset distribution in systemic lupus erythematosus. Clin Exp Immunol. 1991 Nov;86(2):203–206. doi: 10.1111/j.1365-2249.1991.tb05796.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mills J. A. Systemic lupus erythematosus. N Engl J Med. 1994 Jun 30;330(26):1871–1879. doi: 10.1056/NEJM199406303302608. [DOI] [PubMed] [Google Scholar]
- Modlin R. L., Pirmez C., Hofman F. M., Torigian V., Uyemura K., Rea T. H., Bloom B. R., Brenner M. B. Lymphocytes bearing antigen-specific gamma delta T-cell receptors accumulate in human infectious disease lesions. Nature. 1989 Jun 15;339(6225):544–548. doi: 10.1038/339544a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Riccieri V., Spadaro A., Parisi G., Taccari E., Moretti T., Bernardini G., Favaroni M., Strom R. Down-regulation of natural killer cells and of gamma/delta T cells in systemic lupus erythematosus. Does it correlate to autoimmunity and to laboratory indices of disease activity? Lupus. 2000;9(5):333–337. doi: 10.1191/096120300678828460. [DOI] [PubMed] [Google Scholar]
- Robak E., Błoński J. Z., Bartkowiak J., Niewiadomska H., Sysa-Jedrzejowska A., Robak T. Circulating TCR gammadelta cells in the patients with systemic lupus erythematosus. Mediators Inflamm. 1999;8(6):305–312. doi: 10.1080/09629359990315. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- 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]
- 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]