title: CD8+ suppressor cells inhibit staphylococcal protein A-induced gamma interferon production by CD4+ lymphocytes.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Montreal, Quebec, Canada.
authors.forename: S S
authors.initials: SS
authors.lastname: Kasparian
authors.forename: J
authors.initials: J
authors.lastname: Menezes
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens; D003602:Cytotoxicity, Immunologic; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013205:Staphylococcal Protein A / Q000494:pharmacology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D013205:Staphylococcal Protein A; D007371:Interferon-gamma; D015232:Dinoprostone; D007213:Indomethacin