IL-4 IN COMBINATION WITH TGF-BETA FAVORS AN ALTERNATIVE PATHWAY OF TH1 DEVELOPMENT INDEPENDENT OF IL-12

IL-4 was found to be the essential differentiation factor for Th2 cell s and simultaneously to be a potent inhibitor of Th1 development that is induced by IFN-gamma and IL-12, Furthermore, it was demonstrated th at TGF-beta can also inhibit Th1 development, In this work, we demonst rate that polyclonal activation of Mel-14(high)CD4(+) T cells by immob ilized anti-alpha beta TCR mAb together with a mixture of IL-4 and TGF -P can lead to the development of both Th1 and Th2 cells, depending on the concentration of these cytokines, Additional experiments revealed that Th1 induction by a combination of IL-4 and TGF-beta depends on t he presence of endogenous IFN-gamma and that this alternative Th1 deve lopment is further enhanced by IL-12, but is not dependent on this cyt okine. Moreover, naive OVA(323-339)-specific Th cells that were stimul ated by APCs and OVA(323-339) peptide differentiated toward Th1 cells after priming in the presence of IL-4 in combination with TGF-beta. He nce, this finding confirmed the results obtained by polyclonal activat ion of naive CD4(+) Th cells and implicates that this alternative Th1 development may also occur in vivo under the influence of TGF-beta and IL-4 independently of the Th1-promoting effect of IL-12.