GATA-3 significantly downregulates IFN-gamma production from developing Th1 cells in addition to inducing IL4-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 mol ecules. Activation of Stat factors, although specific is a rapid event; how ever, differentiation of Th cells takes place over several days. Thus, it i s unlikely that the expression of effector cytokines is mediated solely by Stat factors. Recently there have been indications that link other molecula r factors to Th subset development. The transcription factor GATA-3 is sele ctively expressed in Th2 cells and has been shown to induce the expression of Th2 cytokines in developin Th1 cells. Using retroviral infection of naiv e T cells to introduce GATA-3 cDNA, we measured its direct effects on the d evelopment of Th1 cytokine production. We now show that ectopic expression of GATA-3 in developing Th1 cells significantly inhibits IFN-gamma, as well as enhancing IL-4 and IL-5 production. Furthermore. GATA-3 inhibits produc tion of IFN-gamma by developing Th1 cells in the complete absence of IL-4. Thus, antagonism of Th1 development by GATA-3 may facilitate rapid divergen ce of Th subsets toward a Th2 phenotype in concert with other factors. (C) 1999 Academic Press.