Inhibition of macrophage-induced antigen-specific T-cell proliferation by interferon-gamma.
The effects of IFN-gamma on macrophage (M phi)-mediated antigen-specific T-cell proliferation was investigated. A well-defined assay system using purified resident populations of antigen-pulsed peritoneal M phi and immune T cells was used to measure M phi-induced antigen-specific T-cell proliferation. Antibody affinity purified or recombinant IFN-gamma inhibited M phi-induced T-cell proliferation when KLH-pulsed M phi from mice given IFN-gamma prior to KLH were cultured with KLH immune T cells from normal mice. Monoclonal rat anti-IFN-gamma antibody neutralized the inhibitory effect of IFN-gamma. This inhibition of T-cell proliferation occurred despite the fact that these M phi appeared to be activated by IFN-gamma 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-gamma has in regulating the immune response.
McKernan
L N
LN
Department of Microbiology and Immunology, Medical College of Pennsylvania, Philadelphia 19129.
Blank
K J
KJ
Spitalny
G L
GL
Murasko
D M
DM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D000939:Epitopes / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D007213:Indomethacin