Signaling pathways that lead to the silencing of the interleukin-4-producing potential in Th1 cells.

In order to develop the most effective Th1 immunity, naïve CD4(+) T cells must acquire the capacity to induce the expression of IFN-gamma and to silence Th2 cytokine-producing potential. Although the IFN-gamma-STAT1 and the IL-12-STAT4 pathways have been demonstrated to be important in inducing the IFN-gamma-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-gamma and the IL-12 pathways in silencing the IL-4-producing potential in Th1 cells. We found that IFN-gamma was essential to silence the IL-4-producing potential in Th1 cells, while IL-12 only partially suppressed the IL-4-producing potential. IFN-gamma 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-gamma-STAT1 pathway converge at the point of T-bet. Our study demonstrates that the IFN-gamma-STAT1-T-bet signaling pathway is the major pathway that leads to silencing the IL-4-producing potential of Th1 cells.