We have previously demonstrated that human natural killer cells are reversibly inhibited by activated monocytes or polymorphonuclear cells through the release of hydrogen peroxide. This provides a mechanism for suppression of natural killing at sites of inflammation. In studies during the first year of this grant we have identified the complement fragment, C3c, as a soluble mediator that triggers this mechanism of suppression by monocytes. During the next year of support, our specific aims are: (1) Examine sera from patients with Sjogren's Syndrome or systemic lupus erythematosus for factors that suppress natural killer activity, with particular regard to whether these factors require the production of reactive oxygen metabolites (RO). Serum factors will be resolved by size using gel-permeation, high-performance liquid chromatography. The role of RO will be examined by removing RO-producing cells (monocytes) and by testing the effect of scavengers of RO, particularly catalase. (2) Develop clones of human NK cells in order to examine directly the effects of RO on the stages of killing by these clones, i.e., target cell binding, initiation of lytic event, lysis. (3) Complete studies on the suppression of T-cell cytotoxicity and of antibody-dependent cell-mediated cytotoxicity by RO and of the initiation of this suppression by the complement fragment, C3c. (SR)