Rats immunized with native but not denatured type II collagen (CII) intradermally develop a polyarthritis with histologic an radiographic manifestations resembling those found in patients with rheumatoid arthritis. This immunologically mediated model appears to be T cell dependent. To characterize the pathogenic and immunoregulatory mechanisms involved in the induction of collagen arthritis, rat T cell lines reactive to type II collagen have been established. Certain lines induce a synovitis when injected intraarticularly (I.A.), protect immunologically intact recipients from the induction of collagen arthritis when administered intravenously (I.V.), and produce an arthritogenic lymphokine. The proposed studies will develop a library of CII-reactive T cell clones from these lines and determine whether disparities in their bioactivity can be attributed to differences in antigen recognition, expression of a particular set of T cell antigen receptors, or arthritogenic lymphokine production. The CII clones will be screened with V gene probes to evaluate whether arthritogenicity is restricted to a limited repertoire of T cell receptors for type II collagen. Since only CII-reactive T cells appear to elaborate an arthritogenic lymphokine, additional experiments will identify the primary structure of this protein and define whether clonal arthritogenicity is inextricably linked to its generation. These studies should expand our understanding of T cell mediated processes in the pathogenesis of a chronic inflammatory synovitis.
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