Antigen-induced human interferon-gamma production. Differential dependence on interleukin 2 and its receptor.
Once stimulated with Toxoplasma gondii or cytomegalovirus (CMV) antigens, peripheral blood mononuclear cells from healthy seropositive donors secrete comparable levels of interferon-gamma (IFN-gamma). Both antigens also stimulated specific production of interleukin 2 (IL-2), a lymphokine believed to be important in IFN-gamma generation. T. gondii antigen, however, induced ninefold more IL-2 than did CMV antigen suggesting different mechanisms for antigen-stimulated IFN-gamma production. Therefore, we examined for both antigens 1) the cellular sources of IL-2 and IFN-gamma, 2) the kinetics of IL-2 production and IL-2 receptor (IL-2R) expression, and 3) the effect of antibodies to IL-2 and IL-2R on IFN-gamma secretion. For both antigens, IL-2 and IFN-gamma secretion was T4+ cell-dependent. T. gondii antigen induced high levels of IL-2 at 24 hr which increased further at 48 hr, and IFN-gamma production was strongly inhibited by antibodies to both IL-2 (90 +/- 2%) and IL-2R (80 +/- 5%). In contrast, CMV antigen stimulated low levels of IL-2 at 24 hr which declined still further by 48 hr, and CMV-stimulated IFN-gamma generation was appreciably less well inhibited by antibodies to IL-2 (47 +/- 2%) and IL-2R (31 +/- 8%). These results suggest the possibility of two mechanisms for antigen-induced IFN-gamma production--one primarily dependent on and the other largely independent of IL-2 and its receptor. Both mechanisms, however, require the activity of sensitized T4+ cells.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D014122:Toxoplasma / Q000276:immunology
D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D000956:Antigens, Viral; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma