GATA-3 Significantly Downregulates IFN-γ Production from Developing Th1 Cells in Addition to Inducing IL-4 and IL-5 Levels

IL-12 and IL-4 are dominant factors driving the development of Th1 and Th2 cells, respectively, by their activation of Stat-4 and Stat-6 signaling molecules. Activation of Stat factors, although specific, is a rapid event; however, differentiation of Th cells takes place over several days. Thus, it is unlikely that the expression of effector cytokines is mediated solely by Stat factors. Recently there have been indications that link other molecular factors to Th subset development. The transcription factor GATA-3 is selectively expressed in Th2 cells and has been shown to induce the expression of Th2 cytokines in developing Th1 cells. Using retroviral infection of naive T cells to introduce GATA-3 cDNA, we measured its direct effects on the development of Th1 cytokine production. We now show that ectopic expression of GATA-3 in developing Th1 cells significantly inhibits IFN-γ, as well as enhancing IL-4 and IL-5 production. Furthermore, GATA-3 inhibits production of IFN-γ by developing Th1 cells in the complete absence of IL-4. Thus, antagonism of Th1 development by GATA-3 may facilitate rapid divergence of Th subsets toward a Th2 phenotype in concert with other factors.