Regulation of IFN-gamma induction in human peripheral blood cells by exogenous and endogenously produced interleukin 2.
Interferon (IFN)-gamma production, stimulated by the addition of exogenous interleukin (IL) 2, T cell mitogens, or tuberculin purified protein derivative (PPD) was studied in cultures of separated human mononuclear cells or unseparated peripheral blood leukocytes (PBL). IFN-gamma was induced by the addition of IL 2 to cultures of otherwise unstimulated cells. The minimal concentration of exogenous IL 2 required to cause a reproducible stimulation of IFN-gamma was about 10 U/ml, i.e., approximately 50 times the minimal concentration required to stimulate proliferation in an IL 2-dependent murine cytotoxic T cell line. Approximately 500 to 1000 IL 2 U/ml were required to produce maximal stimulation of IFN-gamma production in otherwise unstimulated cultures. Monoclonal antibody anti-Tac, specific for an epitope associated with the IL 2 receptor (IL 2 R), inhibited IFN-gamma induction by exogenous IL 2 less strongly than induction by phytohemagglutinin (PHA) or concanavalin A (Con A). The highest degree of inhibition was exerted by anti-Tac on IFN-gamma production stimulated with PPD. Stimulation of IFN-gamma induction by exogenous IL 2 and the inhibitory action of anti-Tac on IFN-gamma production were also seen in cultures of irradiated (2000 R) cells. Treatment of cells with subinducing doses of Con A or phorbol myristate acetate increased IFN-gamma induction by exogenous IL 2. Taken together, the data suggest that endogenously generated IL 2 is a major mediator of IFN-gamma induction in PBL cultures stimulated with antigens or T cell mitogens.
D000911:Antibodies, Monoclonal; D002478:Cells, Cultured; D004274:DNA, Recombinant; D004306:Dose-Response Relationship, Immunologic; D004357:Drug Synergism; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D008934:Mitogens / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000502:physiology*; D015375:Receptors, Interleukin-2
D000911:Antibodies, Monoclonal; D004274:DNA, Recombinant; D007376:Interleukin-2; D008934:Mitogens; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma