Human gamma interferon induction by staphylococcal protein A: effector cells, kinetics and the effect of prostaglandin, indomethacin, ibuprofen and aspirin.
Soluble staphylococcal protein A (SpA) induces the synthesis of gamma-interferon (gamma-IFN) by human peripheral blood lymphocytes (PBL). To investigate the kinetics of this gamma-IFN induction and the effector cells involved, we used a highly purified SpA preparation, PBL from healthy volunteers, and a CPE-inhibition gamma-IFN assay with Sindbis virus in human fibroblasts. The production of SpA-induced gamma-IFN (SpA-gamma-IFN) peaked 48 h after the addition of SpA to cultures of PBL and decreased after 72 h. Subpopulations of PBL were purified by depletion using specific monoclonal antibodies and complement; CD4+ or OKT4+ (T4: helper/inducer) cells were able to produce SpA-gamma-IFN in the absence of CD8+ or OKT8+ (T8: suppressor/cytotoxic) or B-cells. PBL pre-incubated with SpA for more than 72 h inhibited gamma-IFN production by autologous fresh PBL; this inhibition segregated with the T8 subpopulation and was not due to cytotoxicity. SpA-gamma-IFN titers increased markedly when CD3+ or OKT3+ (T3) or T4 cells were incubated with a small number (2-10%) of adherent monocytes, whereas larger numbers (greater than 20%) decreased the yield of SpA-gamma-IFN. This decreased yield was probably mediated by prostaglandin E2 (PGE2) of monocyte origin: the presence of PGE2 was demonstrable in these cultures by radioimmunoassay, and the addition of indomethacin reversed the inhibitory effect of large numbers of monocytes; further, treatment of T-cells with exogenous PGE2 also led to an inhibition of SpA-gamma-IFN. Ibuprofen and aspirin also had an effect comparable to indomethacin on SpA-gamma-IFN production. These observations indicate that the production of SpA-gamma-IFN is by T4 lymphocytes, is enhanced by limited numbers of accessory cells (monocytes), and is also regulated by T8 cells via monocyte PGE2.
Ducatenzeiler
A
A
Department of Microbiology and Immunology, Pediatric Research Centre, Montreal, Quebec, Canada.
Menezes
J
J
D001241:Aspirin / Q000494:pharmacology; D015232:Dinoprostone; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis*; D007700:Kinetics; D009000:Monocytes / Q000276:immunology; D011458:Prostaglandins E / Q000494:pharmacology; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D013205:Staphylococcal Protein A / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism
D011458:Prostaglandins E; D011459:Prostaglandins E, Synthetic; D013205:Staphylococcal Protein A; D007371:Interferon-gamma; D015232:Dinoprostone; D001241:Aspirin; D007052:Ibuprofen; D007213:Indomethacin