Killer-helper effect of L cells in the generation of anti-MM cytotoxic T lymphocytes: replacement by beta-interferon and mechanisms of action.
Cytotoxic T lymphocytes (CTL) for MM tumor cells were generated only when L-MM tumor hybrid (L-FM3A#2)-primed spleen cells were stimulated in vitro with a mixture of mitomycin C-treated parental FM3A/R tumor cells and L cells, but not when they were stimulated with FM3A/R or L cells alone. Killer-helper activity of L cells was replaced by a beta-interferon (IFN) preparation (L-cell IFN). Anti-(alpha + beta)-IFN antibodies completely inhibited the killer-helper activity of L-cell IFN. Several lines of evidence suggested that the killer-helper effect of L-cell IFN resulted from an action at an early step in the generation of anti-MM CTL, as follows. The killer-helper effect of L-cell IFN diminished as the addition was delayed during culture for 5 days. The presence of L-cell IFN during the first 24 hr was enough to generate a maximal CTL response. Anti-(alpha + beta)-IFN antibodies showed no inhibitory activity on the generation of anti-MM CTL when they were added to the culture on day 2 or 4. It was also demonstrated that the killer-helper effect of L-cell IFN resulted from an effect on primed spleen cells, but not from an effect on stimulator cells. Furthermore, it was observed that IFN acted on nylon wool-adherent cells in the generation of anti-MM CTL. Plastic-adherent cells preincubated with L-cell IFN also enhanced the generation of anti-MM CTL when they were added to a culture where primed spleen cells were stimulated with FM3A/R tumor cells. These results suggest that activation of macrophages by L-cell IFN at the initiation step is essential for the generation of anti-MM CTL.
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D002448:Cell Adhesion; D003165:Complement System Proteins / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D007370:Interferon Type I / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology*; D007739:L Cells / Q000276:immunology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology; D009374:Neoplasms, Experimental / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000906:Antibodies; D000951:Antigens, Neoplasm; D007370:Interferon Type I; D008937:Mitomycins; D016685:Mitomycin; D003165:Complement System Proteins