The E receptor regulates interferon-gamma production: four-receptor model for human lymphocyte activation

The E receptor (binds sheep erythrocytes) is found on virtually all human T cells. Here we show that a monoclonal antibody 9.6, which recognizes and binds the E receptor, inhibited interferon-gamma production by human peripheral blood mononuclear leukocytes induced with the mitogens phytohemagglutinin, concanavalin A, Staphylococcal enterotoxin A and the monoclonal antibody OKT3. Metabolic activation (RNA and DNA synthesis) in human peripheral blood mononuclear leukocytes in response to mitogens was also sharply inhibited by 9.6. This inhibitory effect occurred early during the induction phase since 9.6 had much diminished inhibitory effects when added 15-24 h after induction; peak IFN-gamma production and DNA synthesis occurred 3-4 days post induction. An early event inhibited by 9.6 appeared to be interleukin 2 (IL 2) receptor formation since: (a) the ability of mitogen-stimulated peripheral blood mononuclear leukocytes to absorb IL 2 was inhibited by 9.6, and (b) lines of T lymphocytes which already expressed IL 2 receptors were largely resistant to the inhibitory effects of 9.6 on IFN-gamma production and DNA synthesis. The tumor promoters 12-O-tetradecanoyl phorbol-13-acetate and teleocidin largely reversed the inhibition by 9.6 of IFN-gamma production and metabolic activation induced by mitogens. A model for the control of IFN-gamma induction involving four receptors, those for mitogens, tumor promoter, IL 2 and erythrocyte, is proposed.