Immunological reactivity towards chondrocytes in rat and man: relevance to autoimmune arthritis.
Immunological investigation of articular chondrocytes obtained from rat and man have shown the presence of unique differentiation antigens on the cell surface demonstrated by poly- or monoclonal antibodies in both species, and by the analysis of T cell reactivity in the rat. Both species of chondrocytes express Class I antigens in common with all nucleated mammalian cells and, in man, individual specificities of the MHC A, B, and C locus can be identified using standard histocompatibility testing. Class II antigens are strongly expressed in the rat but are expressed poorly in the human specimens we have analyzed. This finding is at variance with the reports of others and may depend upon the antisera we have used or the diseased state of our patient donors. In the rat, T cell reactivity to chondrocyte antigens is strong and can be demonstrated in both proliferation and cytotoxic assay. Moreover, syngeneic reactivity is present in naive animals, suggesting that rats are not tolerant of their own CSDA. The cross-reactivity found on analysis of cytotoxic killing suggests a sharing of differentiation antigens amongst the different strains of rats and possibly a limited polymorphism for this system. In man, conventional assays for T cell reactivity are hampered by the presence of a soluble inhibitor of lymphocyte proliferation released by chondrocytes and as yet unidentified. The poor representation of Class II antigens on our chondrocyte specimens may further contribute to the difficulty in producing proliferation. On the other hand, early success is reported in finding a significant number of T cell clones isolated from the inflammatory membrane of patients with rheumatoid arthritis, which respond to chondrocyte antigens. The possibility that these antigens may play a role in the pathogenesis of inflammatory arthritis may be more readily explored by exploring these approaches.
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Shriners Hospitals for Crippled Children, Immunology Research Laboratory, Honolulu, HI 96826.
D000818:Animals; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D000954:Antigens, Surface; D001168:Arthritis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D002356:Cartilage / Q000166:cytology / Q000276:immunology*; D002478:Cells, Cultured; D003429:Cross Reactions; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D051381:Rats; D011919:Rats, Inbred Strains
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D015395:Histocompatibility Antigens Class I