Destruction of supporting fibrous connective tissue in inflamed periodontium is one of the principal manifestations of human periodontal disease. Thymus (T) and bone marrow (B) derived lymphocytes, activated by plaque antigens, are presumed to participate in the destruction of gingiva fibroblasts through their pharmacologically active lymphokines. Evidence also exists suggesting that appropriately activated human lymphocytes directly destroy human fibroblasts. This project is directed toward determining whether there is a direct cytotoxic effect on human fibroblasts by plaque-stimulated T and B lymphocytes from patients with periodontal disease. In addition, the effect of autologous and homologous sera, containing anti-plaque antibodies, on direct immune cytotoxicity processes will be assessed. The capacity of antibody-antigen aggregates to induce lymphocyte cytotoxicity toward fibroblasts will also be investigated. Information on these direct lymphocyte cytotoxic activities as well as those caused by lymphotoxin released by plaque antigen activated lymphocytes will be correlated with plaque-induced lymphocyte blastogenesis and lymphokine production levels, thus further defining the immunological T and B cell roles in destructive human periodontal disease.