Cellular origin and interactions involved in gamma-interferon production induced by OKt3 monoclonal antibody.
OKT3 monoclonal antibody, a human T cell mitogen, induced interferon production by cultured mononuclear cells at 10(-11) M concentrations. Interferon was secreted only under conditions wherein OKT3 was mitogenic, and production was correlated with cell proliferation. Thus, like mitogenesis, interferon secretion reached a peak 3 days after OKT3 stimulation, was inhibited by a factor(s) in human serum, and required 1000 times higher concentrations of Fab and F(ab')2 fragments of OKT3 for induction. The interferon was most likely of "gamma" (immune) type, because pH 2 and 56 degrees C treatments denatured it, whereas anti-alpha or -beta interferon antibodies did not. Mononuclear cells were fractionated into subpopulations that contained OKT4+ cells (helper/inducer T cells), OKT8+ cells (cytotoxic/suppressor T cells), and OKM1+ cells (monocytes) by combining sheep red blood cell rosetting and complement-mediated lysis using monoclonal antibodies against specific cell types. Both OKT4+ and OKT8+ cells proliferated upon OKT3 stimulation with the absolute requirement of OKM1+ cells. However, OKT4+ cells plus OKM1+ cells were necessary for the secretion of interferon. Studies with selective pretreatments with mitomycin C suggested that gamma-interferon was secreted by the OKT4+ cells and that the OKM1+ population subserved an accessory function.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002450:Cell Communication; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007372:Interferons / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008937:Mitomycins / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology
D000911:Antibodies, Monoclonal; D008937:Mitomycins; D004247:DNA; D007372:Interferons