IMMUNOPATHOGENESIS OF ARTHRITIS IN MRL MICE

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Autoimmune MRL-1pr mice develop an arthropathy with clinical and histological features in common with rheumatoid arthritis (RA). To elucidate the immunopathogenesis of this spontaneous disease model, it is proposed to identify effector mechanisms through genetic and cellular analysis. 1pr congenic mice and informative F1 and F2 generations will be studied to determine whether 1pr is itself sufficient for arthritis or requires interaction with other genes. To assess cellular mechanisms of disease, MRL- 1pr mice will be treated with various immunomodulatory agents such as monoclonal antibodies to L3T4 and Ia antigens. The nature of the cells infiltrating the synovium in both untreated and treated mice will then be investigated using immunohistologic techniques to characterize cell surface markers. The production of cytokines will also be evaluated in the synovium by in situ hybridization using probes for various mediators that have been postulated to promote joint changes. Finally, findings with MRL- 1pr mice will be compared with those observed in mice with collagen-induced arthritis, a model in which the role of T-cells is more defined. Together, these studies should help elucidate important facets of MRL-1pr arthritis and help assess its relationship to processes occurring in the RA joint.