a) Further development was completed on a bioassay for IL-4 which is dependent upon upregulation of CD23 expression on a subclone of the B cell line Ramos selected for sensitivity and magnitude of this response. TNFs alpha and beta were found to have minor effects on the assay and to synergize with IL-4 in their effects. The assay has a sensitivity of about 50pg/ml, favorable compared to other published assays, insufficiently sensitive to detect L-4 in various supernatants of cultured lymphocytes tested. b) studies on the effects of IL-4 on cytotoxicity continued. It was observed that while IL-4 inhibits development of LAK activity, it augments development of cytotoxicity vs. LAK sensitive targets in mixed lymphocyte cultures. Mechanisms are under study. c) studies of the effects of IL-7 on CTL development were performed in influenza-specific alloantigen-specific and lectin-dependent systems. All systems indicate that IL-7 could upregulate both proliferation and, to a far greater extent, cytotoxicity (up to 80 fold). When IL-7 was added to cultures within 2-3 days of their termination, significant upregulation of cytotoxicity could be observed in the presence of only minimal effects on proliferation. This indicates that IL-7 can function as a CTL differentiation factor. The alloantigen for specific cytotoxicity upregulated by IL-7 was mediated by CD8+ cells to upregulate lectin- dependent cytotoxicity. Experiments with anti-IL-7 suggested that endogenous production of IL-7 was occurring in mixed lymphocyte cultures and accounted for some of the s cytotoxicity observed Current studies are aimed at development of cell clones to study IL-y effects and to detect IL- 7 messenger RNA or protein in the cells and supernatants studied. Also, with Dr. Eda Bloom, studies are underway to look at IL-7 effects on expression of serine esterase and perforin genes.
