INTERLEUKIN-12 ACTS DIRECTLY ON CD4-CELLS TO ENHANCE PRIMING FOR INTERFERON-GAMMA PRODUCTION AND DIMINISHES INTERLEUKIN-4 INHIBITION OF SUCH PRIMING( T)

Naive CD4+ T cells produce interleukin 2 (IL-2) but little IL-4 or int erferon gamma (IFN-gamma). In vitro, they develop into IL-4 or IFN-gam ma producers depending on the conditions of the priming culture. Using T-cell receptor transgenic CD4+ T cells, the role of IL-12 and IL-4 i n antigen-specific printing was examined. IL-12 substantially enhanced the ability of naive CD4+ T cells to develop into cells that produced IFN-gamma upon restimulation. However, it was not essential since ant i-IL-12 antibodies failed to block the priming for IFN-gamma observed in the absence of exogenous IL-12. When both IL-12 and IL-4 were prese nt in the priming culture, IL-12 did not inhibit priming for IL-4 prod uction. In contrast, IL-4 diminished but did not abolish priming for I FN-gamma production. In an accessory cell-independent priming system, IL-12 strikingly augmented priming for IFN-gamma production, indicatin g that it acts directly on T cells. IFN-gamma itself did not enhance p riming for IFN-gamma production in either accessory cell-dependent or independent systems. In an accessory cell-dependent system, the IL-12- mediated enhancement was not blocked by adding neutralizing anti-IFN-g amma monoclonal antibody. However, in an accessory cell-independent sy stem, anti-IFN-gamma antibody did inhibit priming for IFN-gamma produc tion leaving open a role for IFN-gamma in the priming process. These d ata indicate that IL-12 has a major effect on the inductive phase of T -cell priming by enhancing commitment to IFN-gamma production and thus can profoundly influence the state of immunity that develops.