The overall objectives of the proposed work are to learn more of the possible significance of K cell cytotoxicity in the rheumatic diseases and related conditions. K cell cytotoxicity involves the cytotoxic action of non-immune lymphoid cells upon target cells sensitized by specific antibody. This mechanism may operate in such divergent conditions as Hashimoto's thyroiditis, transitional cell carcinoma of the bladder, rejection of kidney grafts, and immunity to microbial agents. We recently have described alteration in K cell function in the peripheral blood of patients with systemic lupus erythematosus. This information, together with data that K cell activity is modulated by immune complexes, anti-immunoglobulins, and immunosuppressive therapy, would indicate that further studies in immunologically mediated diseases are warranted. In clinical studies, we will investigate correlations of various laboratory and clinical parameters with K cell function. Additionally, in in vitro studies, we will determine the possible role of lymphocytotoxic antibodies, immune complexes, and rheumatoid factor on the system, and investigate possible implications of K cells as cytotoxic cells in dermatomyositis and hemolytic anemia in systemic lupus erythematosus. BIBLIOGRAPHIC REFERENCES: Hirsen, D., S.M. Cooper and G.J. Friou. Lymphocyte defect in ADCMC of patients with SLE. Clin Res, April, 1977. Cooper, S.M., J.P. Girves, D.J. Hirsen and G.J. Friou. Spontaneous cell-mediated cytotoxicity (SCMC) by non-thymus derived lymphocytes. Clin Res 25:117A, 1977.