Rheumatoid arthritis is an autoimmune disease characterized by T-cell infiltration of the synovium of joints. Analysis of the phenotype and antigen specificity of the infiltrating cells may thus provide insight into the pathogenesis of rheumatoid arthritis. T cells were cloned with interleukin 2, a procedure that selects for in vivo-activated cells. All clones had the CD4 CDW29 phenotype. Their antigen specificity was tested by using a panel of candidate joint autoantigens. Four of 17 reacted against autologous blood mononuclear cells. Two clones proliferated in response to collagen type II. After 21 months, another set of clones was derived from synovial tissue of the same joint. One of eight clones tested showed a strong proliferative response against collagen type II. The uncloned synovial T cells of a third operation from another joint also responded to collagen type II. The persistence of collagen type II-specific T cells in active rheumatoid joints over a period of 3 years suggests that collagen type II could be one of the autoantigens involved in perpetuating the inflammatory process in rheumatoid arthritis.Rheumatoid arthritis is a chronic inflammatory disease of synovial joints leading to destruction of cartilage and erosion of bone (1). Currently, the mechanisms underlying the perpetuation of the chronic inflammation and the consequent tissue damage are poorly understood. It is widely considered that the immune system is a major participant in these processes, perhaps through the activation of complement by immune complexes containing rheumatoid factor (2) or by activated immunocompetent cells (3) releasing protein mediators such as interleukin 1 (IL-1), tumor necrosis factor, and interferon-y.Study of cell-surface markers and cellular organization has shown that there is a predominance of T lymphocytes in the synovial infiltrate (4) Here we report the cloning of the activated T cells from a patient with active erosive rheumatoid arthritis. In two operative samples, 21 months apart, collagen type II-specific clones were detected at a frequency of -'12%. In a third sample, the uncloned joint T cells also responded to collagen type II. This persistent response suggests a possible role of these T cells in maintaining the chronic inflammatory state in rheumatoid arthritis, since in these joints there is abundant HLA class II and collagen type II available to restimulate the T cells. MATERIALS AND METHODS Patient. C.L., a Caucasian female (HLA DR-1,-6), developed polyarthritis diagnosed as rheumatoid arthritis in 1975.Laboratory investigations have shown a consistent lack of IgM rheumatoid factor. There was a low titer of anti-nuclear antibody with activity against DNA-histone and singlestranded DNA. She was treated with gold salts. After 4 years, she relapsed with severe symptoms. A right knee synovectomy was performed, which was the source of the first cloning procedure; 21 months later, because of severe pain, cartilage damage, and loss of mobility, a knee prosthesis was inserted, providing the s...

The clonality of T lymphocytes isolated from the synovial fluid and peripheral blood of patients with rheumatoid arthritis was investigated by restriction enzyme fragment mapping of the rearrangements of the beta chain gene of the T-cell antigen receptor. Three patients showed a dominant rearrangement amongst their synovial fluid T cells which was not seen in their peripheral blood T-cell population, suggesting the presence of a predominating T-cell clone. However, most of the patients examined (8 out of 11) demonstrated polyclonal T-cell populations in both their synovial fluid and peripheral blood. Of four synovial fluid T-cell lines investigated, one showed evidence of a dominant T-cell clone.

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