Roles of IFN-γ and IFN-α in IL-12-induced T helper cell-1 development

IL-12 and IL-4 direct T cell development toward Th1 and Th2 phenotypes, respectively. While IFN-γ and IFN-α have been reported to regulate Th1 development as well, the mechanism and cellular locus of their effects are unclear. In this study, we use a TCR-transgenic system to examine the actions of these cytokines on CD4⁺ T cell phenotype development. We find that neither IFN-γ nor IFN-α can induce Th1 development alone. However, IFN-γ can significantly augment IL-12 priming for subsequent IFN-γ production by T cells. Interestingly, lymphocyte endothelial cell adhesion molecule-1(bright) (naive) T cells require IFN-γ during primary activation for maximal IL-12- induced Th1 development, whereas lymphocyte endothelial cell adhesion molecule-1(dull) (memory) T cells do not. IFN-α only partially substitutes for IFN-γ in promoting IL-12-induced Th1 development. When the endogenous IFN-γ present in primary T cell cultures is neutralized, IFN-α treatment augments IL-12-induced effects on inhibition of subsequent IL-4 production, but fails to significantly enhance IL-12 priming for subsequent IFN-γ production. Thus, our data suggest that IFN-γ provides a direct costimulatory signal to T cells to up-regulate IL-12-induced Th1 development and may operate by inducing IL-12 responsiveness in naive T cells.