REGULATION MECHANISM BETWEEN CELL-MEDIATED AND HUMORAL IMMUNE RESPONSE TO MM-ANTIGEN

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WE HAVE REPORTED THAT SOMATIC TUMOR HYBRID OF L CELL WITH MM TUMOR CELL WHICH ALONE FAILED TO INDUCE CYTOTOXIC T CELLS (CTL) BUT ANTIBODIES TO MM ANTIGEN IN SYNGENEIC MICE, COULD INDUCE MM-SPECIFIC CTL AND THAT INTERACTION OF UNPRIMED SYNGENEIC SPLEEN CELLS WITH L CELLS RELEASED KILLER-HELPER FACTOR(S) WHICH PLAYS AN IMPORTANT ROLE IN CTL GENERATION, AND MOUSE BETA-INTERFERON (IFN) COULD SUBSTITUTE IT. BASED ON THESE RESULTS, THE FOLLOWING RESULTS WERE OBTAINED IN A SERIES OF EXPERIMENTS: I. KILLER-HELPER EFFECT OF MOUSE BETA-IFN IN THE SECONDARY CTL GENERATION IN VITRO; MAXIMAL MM-SPECIFIC CTL (THY- <1^+> , LYT- <2^+> ) GENERATION WAS OBSERVED IN THE PRESENCE OF IFN DURING THE FIRST 24-HR CULTURE AND THE EFFECT OF IFN WAS COMPLETELY INHIBITED BY SPECIFIC ANTI-IFN ANTIBODY. MACROPHAGES IN RESPONDER CELL POPULATION WERE TARGETS FOR ACTION OF IFN. II. KILLER-HELPER FACTOR(S); ISOLATION OF THE FACTOR(S) WAS UNSUCCESSFUL. ACTIVITIES OF CSF, IFN AND IL-3, EXCEPT IL-2 WERE PRESENT IN CELL-FREE CULTURE SUPERNATANTS CONTAINING KILLER-HELPER FACTOR(S), BUT ONLY IFN ACTIVITY SEEMED TO BE RELATED WITH HELPER ACTIVITY. GAMMA-IFN WAS SUGGESTED BECAUSE OF LOSS OF ACTIVITY BY PH 2 TREATMENT, BUT MOUSE RECOMBINANT GAMMA-IFN WAS INACTIVE AS KILLER-HELPER FACTOR. III. EFFECT OF L CELLS ON ANTIBODY RESPONSE; THERE WAS NO DIFFERENCE IN THE CAPACITY FOR HELPER T CELL INDUCTION IN ANTI-TNP ANTIBODY RESPONSE BETWEEN MM TUMOR AND HYBRID CELLS. IV. KILLER-HELPER EFFECT OF L CELLS IN THE PRIMARY CTL GENERATION: CTL WERE NOT PODUCED BY STIMULATION WITH HEATED (47゜, 60 MIN) ALLOGENEIC CELLS IN THE ABSENCE BUT PRESENCE OF L CELLS. THE FACTOR CONTAINING CULTURE SUPERNATANT OR BETA-IFN ALSO SHOWED HELPER ACTIVITY IN THIS SYSTEM AND ACTED AT THE EARLY STEP OF CTL GENERATION. REMOVAL OF ASIALO- <GM1^+> CELLS FROM THE RESPONDER POPULATION FAILED TO INDUCE ALLO-CTL EVEN IN THE PRESENCE OF L CELLS.