In some recent studies on rheumatoid arthritis patients, the principal investigators and their collaborators found an unexpected aberration in peripheral blood Vbeta use. Many of the patients studied had undetectable or very low percentages of T cells in their peripheral blood using the T cell receptor Vbeta, Vbeta14. This was not found in any normal individuals, even individuals who, like the patients, expressed DR4. By contrast Vbeta14-bearing T cells were found at high levels in the synovial fluids of the rheumatoid patients. This led the investigators to suggest that a Vbeta14-specific superantigen might be involved in the pathogenesis of rheumatoid arthritis, simultaneously deleting Vbeta14-bearing cells in peripheral blood, and stimulating autoantigen specific Vbeta14-bearing T cells in joints. The investigators now propose to test these ideas in experimental models in mice. They have shown that chronic exposure to a superantigen causes the deletion of target T cells in these animals. They will not investigate the consequences of simultaneous exposure of mice to a superantigen and a conventional antigen which react with T cells bearing the same Vbeta. The effects of agents such as adjuvants on this simultaneous exposure will also be examined. Results of these experiments will be applied to a second set of studies, on the interaction between superantigen and an autoantigen, known to involve T cells bearing the same Vbeta. The overall goal of these experiments is to understand how some antigens cause death, and others, activation of T cells, and also to establish whether or not superantigens may contribute to the induction or maintenance of autoimmune diseases.

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