Gα12 is critical for TCR-induced IL-2 production and differentiation of T helper 2 and T helper 17 cells

Abstract

G12 family have been known to modulate a variety of cellular events such as cell migration, B cell activation and maturation, cytokine production, and cell differentiation. In particular, Gα12 modulates IgG production, thus induces IgG antibody-mediated immune responses. However, it is largely unknown whether Gα12 is required for T cell-mediated immune functions. In this study, we investigated the effects of Gα12 in the activation and differentiation of CD4+ T cells. While PMA plus ionomycin induced equal levels of IL-2 production in WT and Gα12-deficient lymphocytes, TCR-triggered IL-2 production was significantly attenuated in Gα12 KO lymphocytes. In particular, CD4+ T cells and effector Th cells lacking of Gα12 revealed diminished IL-2 production, but not IFNγ production, upon TCR stimulation. In addition, supplement of IL-2 preferentially induced Gα12-deficient CD4+ T cells into Th2 and Th17 cells; however, the expression of specific transcription factors was unchanged in Gα12 KO Th cells. While IL-2 expression was still diminished by the re-stimulation with anti-CD3, PMA plus ionomycin restored IL-2 production in Gα12-deficient Th1 and Th2 cells. These results suggest that Gα12 may be a critical signaling molecule in TCR-induced IL-2 production and also relay a signal to suppress Th2 and Th17 cell differentiation. © 2010 Elsevier Inc. All rights reserved.