In order to develop the most effective Th1 immunity, naïve CD4+ T cells must acquire the capacity to induce the expression of IFN-γ and to silence Th2 cytokine-producing potential. Although the IFN-γ-STAT1 and the IL-12-STAT4 pathways have been demonstrated to be important in inducing the IFN-γ-producing capacity in Th1 cells, their respective roles in silencing the IL-4-producing potential in Th1 cells remain unclear. In this study, we investigated the role of the IFN-γ and the IL-12 pathways in silencing the IL-4-producing potential in Th1 cells. We found that IFN-γ was essential to silence the IL-4-producing potential in Th1 cells, while IL-12 only partially suppressed the IL-4-producing potential. IFN-γ depended on STAT1 and IL-12 depended on STAT4 to suppress the IL-4-producing potential. We showed that the IL-12-STAT4 pathway and the IFN-γ-STAT1 pathway converge at the point of T-bet. Our study demonstrates that the IFN-γ-STAT1-T-bet signaling pathway is the major pathway that leads to silencing the IL-4-producing potential of Th1 cells.
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