Role of the guanosine triphosphatase Rac2 in T helper 1 cell differentiation

T helper 1 (T(H)1) cells mediate cellular immunity, whereas T(H)2 cells potentiate antiparasite and humoral immunity. We used a complementary DNA subtraction method, representational display analysis, to show that the small guanosine triphosphatase Rac2 is expressed selectively in murine T(H)1 cells. Rac induces the interferon-gamma (IFN-gamma) promoter through cooperative activation of the nuclear factor kappa B and p38 mitogen-activated protein kinase pathways. Tetracycline-regulated transgenic mice expressing constitutively active Rac2 in T cells exhibited enhanced IFN-gamma production. Dominant-negative pac inhibited IFN-gamma production in murine T cells. Moreover, T cells from Rac2(-/-) mice showed decreased IFN-gamma production under T(H)1 conditions in vitro. Thus, Rac2 activates T(H)1-specific signaling and IFN-gamma gene expression.