Activation of macrophage tumor cytotoxicity by the synergism of two T cell-derived lymphokines: immune interferon (IFN-gamma) and macrophage cytotoxicity-inducing factor 2 (MCIF2).
This report describes the role of T cell-derived lymphokines in induction of macrophage (M phi) tumor cytotoxicity. M phi tumor cytotoxicity was tested with the murine M phi-like tumor PU5-1.8. This M phi-like tumor reacts to stimulation with T cell-derived lymphokines and shows tumor cytotoxicity comparable to resident peritoneal M phi. The experiments demonstrate that immune interferon (IFN-gamma) secreted by T cell clones in limiting dilution microcultures was insufficient to induce M phi tumor cytotoxicity. Induction of M phi tumor cytotoxicity by T cell-derived supernatants with quantities of IFN-gamma undetectable in the IFN assay, however, was completely inhibited by an antiserum raised against recombinant IFN-gamma. Taken together, these results could be thus explained: (a) a T cell-derived lymphokine distinct from but serologically cross-reactive with IFN-gamma induces M phi tumor cytotoxicity, and (b) IFN-gamma activity in supernatants positive for induction of M phi tumor cytotoxicity escapes detection in the IFN assay but can still be inhibited by the anti-IFN-gamma antiserum in the M phi tumor cytotoxicity assay. The latter explanation requires positive evidence for another T cell-derived lymphokine inducing M phi tumor cytotoxicity together with IFN-gamma. This lymphokine was found in the supernatant of T cells in limiting dilution cultures and a long-term T cell clone and was called M phi cytotoxicity-inducing factor 2 (MCIF2). MCIF2 synergizes with IFN-gamma in induction of M phi tumor cytotoxicity; IFN-gamma and MCIF2 alone were ineffective.
D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D002474:Cell-Free System; D003602:Cytotoxicity, Immunologic; D004357:Drug Synergism; D005260:Female; D007106:Immune Sera / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology / Q000302:isolation & purification / Q000502:physiology*; D008222:Lymphokines / Q000096:biosynthesis / Q000302:isolation & purification / Q000502:physiology*; D008262:Macrophage Activation; D016215:Macrophage-Activating Factors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000378:metabolism*
D007106:Immune Sera; D008222:Lymphokines; D016215:Macrophage-Activating Factors; D007371:Interferon-gamma