Abstract
Blood lymphocytes from 37 patients with systemic sclerosis were characterised using monoclonal antibodies in a two colour flow cytometric (fluorescence activated cell sorter (FACS)) analysis. The ratio of helper CD4+ to suppressor/cytotoxic CD8+ T cells was raised in patients compared with that in 30 healthy controls owing to decreased CD8+ cells. In the patients CD4+ and CD8+ cells displayed an increased expression of the activation marker HLA-DR. The relative number of CD11b+ CD8+ lymphocytes (suppressor T cells) was normal, but the calculated absolute counts of this cell type were slightly reduced. The proportions and absolute numbers of suppressor inducer T cells, defined as CD45R+ CD4+ cells, were on average only half the levels observed in controls. These findings were not related to the inflammatory activity as measured by acute phase plasma proteins or serum immunoglobulins. Activated T cells were seen at all stages of the sclerotic process and especially during the early stages of the disease and in patients who had suffered occupational exposure to silica dust. A high proportion of activated T cells was also linked with impaired small intestine function but not with the degree of skin or lung involvement. A loss of suppressor inducer T cells was more pronounced later in the disease and in patients with the CREST (calcinosis, Raynaud's phenomenon, oesophageal dysmotility, sclerodactyly, telangiectasia) syndrome. These data provide further evidence for an involvement of T cell mediated immunity in the perpetuation of systemic sclerosis.
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- Akbar A. N., Terry L., Timms A., Beverley P. C., Janossy G. Loss of CD45R and gain of UCHL1 reactivity is a feature of primed T cells. J Immunol. 1988 Apr 1;140(7):2171–2178. [PubMed] [Google Scholar]
- Alarcón-Segovia D., Palacios R., Ibáez de Kasep G. Human postthymic precursor cells in health and disease. VII. Immunoregulatory circuits of the peripheral blood mononuclear cells from patients with progressive systemic sclerosis. J Clin Lab Immunol. 1981 May;5(3):143–148. [PubMed] [Google Scholar]
- Emery P., Gentry K. C., Mackay I. R., Muirden K. D., Rowley M. Deficiency of the suppressor inducer subset of T lymphocytes in rheumatoid arthritis. Arthritis Rheum. 1987 Aug;30(8):849–856. doi: 10.1002/art.1780300802. [DOI] [PubMed] [Google Scholar]
- Fleischmajer R., Perlish J. S., Reeves J. R. Cellular infiltrates in scleroderma skin. Arthritis Rheum. 1977 May;20(4):975–984. doi: 10.1002/art.1780200410. [DOI] [PubMed] [Google Scholar]
- Freundlich B., Jimenez S. A. Phenotype of peripheral blood lymphocytes in patients with progressive systemic sclerosis: activated T lymphocytes and the effect of D-penicillamine therapy. Clin Exp Immunol. 1987 Aug;69(2):375–384. [PMC free article] [PubMed] [Google Scholar]
- Gupta S., Malaviya A. N., Rajagopalan P., Good R. A. Subpopulations of human T lymphocytes. IX. Imbalance of T cell subpopulations in patients with progressive systemic sclerosis. Clin Exp Immunol. 1979 Nov;38(2):342–347. [PMC free article] [PubMed] [Google Scholar]
- Hafler D. A., Fox D. A., Manning M. E., Schlossman S. F., Reinherz E. L., Weiner H. L. In vivo activated T lymphocytes in the peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. N Engl J Med. 1985 May 30;312(22):1405–1411. doi: 10.1056/NEJM198505303122201. [DOI] [PubMed] [Google Scholar]
- Hedenström H., Malmberg P., Agarwal K. Reference values for lung function tests in females. Regression equations with smoking variables. Bull Eur Physiopathol Respir. 1985 Nov-Dec;21(6):551–557. [PubMed] [Google Scholar]
- Jackson R. A., Morris M. A., Haynes B. F., Eisenbarth G. S. Increased circulating Ia-antigen-bearing T cells in type I diabetes mellitus. N Engl J Med. 1982 Apr 1;306(13):785–788. doi: 10.1056/NEJM198204013061305. [DOI] [PubMed] [Google Scholar]
- Karlsson-Parra A., Tötterman T. H., Nyberg A., Mendel-Hartvig I., Löf L., Forsum U. Immunological effects of ciclosporin in primary biliary cirrhosis: suppression of activated T cells and autoantibody levels. Int Arch Allergy Appl Immunol. 1987;83(3):256–264. doi: 10.1159/000234305. [DOI] [PubMed] [Google Scholar]
- Keystone E. C., Lau C., Gladman D. D., Wilkinson S., Lee P., Shore A. Immunoregulatory T cell subpopulations in patients with scleroderma using monoclonal antibodies. Clin Exp Immunol. 1982 May;48(2):443–448. [PMC free article] [PubMed] [Google Scholar]
- Landay A., Gartland G. L., Clement L. T. Characterization of a phenotypically distinct subpopulation of Leu-2+ cells that suppresses T cell proliferative responses. J Immunol. 1983 Dec;131(6):2757–2761. [PubMed] [Google Scholar]
- Ledbetter J. A., Evans R. L., Lipinski M., Cunningham-Rundles C., Good R. A., Herzenberg L. A. Evolutionary conservation of surface molecules that distinguish T lymphocyte helper/inducer and cytotoxic/suppressor subpopulations in mouse and man. J Exp Med. 1981 Feb 1;153(2):310–323. doi: 10.1084/jem.153.2.310. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morimoto C., Hafler D. A., Weiner H. L., Letvin N. L., Hagan M., Daley J., Schlossman S. F. Selective loss of the suppressor-inducer T-cell subset in progressive multiple sclerosis. Analysis with anti-2H4 monoclonal antibody. N Engl J Med. 1987 Jan 8;316(2):67–72. doi: 10.1056/NEJM198701083160202. [DOI] [PubMed] [Google Scholar]
- Morimoto C., Letvin N. L., Distaso J. A., Aldrich W. R., Schlossman S. F. The isolation and characterization of the human suppressor inducer T cell subset. J Immunol. 1985 Mar;134(3):1508–1515. [PubMed] [Google Scholar]
- Morimoto C., Reinherz E. L., Borel Y., Schlossman S. F. Direct demonstration of the human suppressor inducer subset by anti-T cell antibodies. J Immunol. 1983 Jan;130(1):157–161. [PubMed] [Google Scholar]
- Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. A monoclonal antibody reactive with the human cytotoxic/suppressor T cell subset previously defined by a heteroantiserum termed TH2. J Immunol. 1980 Mar;124(3):1301–1307. [PubMed] [Google Scholar]
- Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. Separation of functional subsets of human T cells by a monoclonal antibody. Proc Natl Acad Sci U S A. 1979 Aug;76(8):4061–4065. doi: 10.1073/pnas.76.8.4061. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roumm A. D., Whiteside T. L., Medsger T. A., Jr, Rodnan G. P. Lymphocytes in the skin of patients with progressive systemic sclerosis. Quantification, subtyping, and clinical correlations. Arthritis Rheum. 1984 Jun;27(6):645–653. doi: 10.1002/art.1780270607. [DOI] [PubMed] [Google Scholar]
- Rozental M., Tomaszewski L. Die Orzin - Ultramikromethode zur Bestimmung der d-Xylose in Blut and Harn. Z Med Labortech. 1975;16(4):191–196. [PubMed] [Google Scholar]
- Steen V. D., Powell D. L., Medsger T. A., Jr Clinical correlations and prognosis based on serum autoantibodies in patients with systemic sclerosis. Arthritis Rheum. 1988 Feb;31(2):196–203. doi: 10.1002/art.1780310207. [DOI] [PubMed] [Google Scholar]
- Sternberg E. M. Pathogenesis of scleroderma: the interrelationship of the immune and vascular hypotheses. Surv Immunol Res. 1985;4(1):69–80. doi: 10.1007/BF02918588. [DOI] [PubMed] [Google Scholar]
- Tan E. M., Rodnan G. P., Garcia I., Moroi Y., Fritzler M. J., Peebles C. Diversity of antinuclear antibodies in progressive systemic sclerosis. Anti-centromere antibody and its relationship to CREST syndrome. Arthritis Rheum. 1980 Jun;23(6):617–625. doi: 10.1002/art.1780230602. [DOI] [PubMed] [Google Scholar]
- Yu D. T., Winchester R. J., Fu S. M., Gibofsky A., Ko H. S., Kunkel H. G. Peripheral blood Ia-positive T cells. Increases in certain diseases and after immunization. J Exp Med. 1980 Jan 1;151(1):91–100. doi: 10.1084/jem.151.1.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ziegler V., Haustein U. F., Mehlhorn J., Münzberger H., Rennau H. Quarzinduzierte Sklerodermie. Sklerodermie-ähnliches Syndrom oder echte progressive Sklerodermie? Dermatol Monatsschr. 1986;172(2):86–90. [PubMed] [Google Scholar]
- Zoumbos N. C., Gascón P., Djeu J. Y., Trost S. R., Young N. S. Circulating activated suppressor T lymphocytes in aplastic anemia. N Engl J Med. 1985 Jan 31;312(5):257–265. doi: 10.1056/NEJM198501313120501. [DOI] [PubMed] [Google Scholar]