CD8+ suppressor cells inhibit staphylococcal protein A-induced gamma interferon production by CD4+ lymphocytes

We have previously demonstrated that purified soluble staphylococcal protein A (SpA) induces the synthesis of gamma interferon (gamma-IFN) by human peripheral blood lymphocytes (PBL), that CD4+ (T helper) cells represent the subpopulation responsible for this synthesis and that prostaglandin E2 (PGE2)-activated CD8+ (T suppressor/cytotoxic) cells have an inhibitory effect on this synthesis. The mechanisms implicated in this regulation remain to be defined, and could involve direct cell-to-cell contact among members of these subpopulations or may be due to a soluble mediator release by CD8+ suppressor cells. In this study, we explored the ability of PGE2 to activate CD8+ cells into either cytotoxic or suppressor cells and the mechanisms by which these cells regulate the SpA-induced gamma-IFN production by CD4+ cells. Peripheral blood lymphocytes from 18 healthy volunteers, prepared by centrifugation over Ficoll-Hypaque gradient, were separated into subpopulations by passage on nylon wool columns and selective depletion using specific monoclonal antibodies and rabbit complement. CD4+ cells were incubated with SpA for gamma-IFN production and CD8+ cells were incubated with 10(-6) M PGE2. After 48 h these populations were remixed and the cytotoxic or suppressor effector function of CD8+ cells was measured. No cytotoxic activity was detected against CD4+ cells. Different levels of suppression of gamma-IFN production were observed in our subjects. Suppression mediated through the release of soluble factor was observed in only 2 of the 18 cases. Taken together, these results suggest that in the present experimental system, the regulation of gamma-IFN production is mediated by suppressor CD8+ T cells and that cell-to-cell contact between both subpopulations is usually necessary.