Inhibition of macrophage-induced antigen-specific T-cell proliferation by interferon-γ

Abstract The effects of IFN-γ on macrophage (Mφ)-mediated antigen-specific T-cell proliferation was investigated. A well-defined assay system using purified resident populations of antigen-pulsed peritoneal Mφ and immune T cells was used to measure Mφ-induced antigen-specific T-cell proliferation. Antibody affinity purified or recombinant IFN-γ inhibited Mφ-induced T-cell proliferation when KLH-pulsed Mφ from mice given IFN-γ prior to KLH were cultured with KLH immune T cells from normal mice. Monoclonal rat anti-IFN-γ antibody neutralized the inhibitory effect of IFN-γ. This inhibition of T-cell proliferation occurred despite the fact that these Mφ appeared to be activated by IFN-γ treatment as measured by increased tumoricidal activity. The mechanism for the inhibition was unrelated to class II (Ia) expression, IL-1 secretion, and prostaglandin secretion. These results demonstrate the complex and sensitive role IFN-γ has in regulating the immune response.