This project proposes to continue efforts to investigate the role of autoimmune responses to collagen in the pathogensis of connective tissue diseases. The rationale for this project is based on the increasing evidence that the articular manifestations of rheumatoid arthritis are, in part, attributable to T cell mediated processes. To elucidate more precisely the cellular immune mechanisms contributing to the induction of arthritis in rats or mice immunized with type II collagen, studies are planned to partially purify a lymphokine induced by type II collagen which is arthritogenic in rats and mice - arthritogenic factor. Other studies will attempt to analyze the T-cell repertoire to type II collagen in rats by cloning techniques. Additional experiments will further assess the possible involvement of hypersensitivity to type II collagen in the pathogenesis of adjuvant arthritis by ascertaining the cellular origin and biochemical and functional nature of the collagen induced arthritogenic factor activity present in this model. By identifying antigen-specific cellular effector mechanisms in animal models of inflammatory arthritis, these studies have the potential to elucidate pathways that may operate and be susceptible to modification in human disease.
| Shmerling, R H; Parker, J A; Johns, W D et al. (1990) Measurement of joint inflammation in rheumatoid arthritis with indium-111 chloride. Ann Rheum Dis 49:88-92 |
| Breedveld, F C; Dynesius-Trentham, R; de Sousa, M et al. (1989) Collagen arthritis in the rat is initiated by CD4+ T cells and can be amplified by iron. Cell Immunol 121:1-12 |
