GADD45γ mediates the activation of the p38 and JNK MAP kinase pathways and cytokine production in effector TH1 cells

The p38 and JNK stress-activated MAPK signal transduction pathways are activated by T cell receptor (TCR) signaling and are required for IFN-gamma production by T(H)1 effector cells. Here, we show that the expression of GADD45 gamma is induced during T cell activation and that the level of expression is higher in TH1 cells than in T(H)2 cells. T(H)1 cells from GADD45 gamma (-1-) mice are severely compromised in their abilities to activate p38 and JNK in response to TCR signaling, produce much less IFN-gamma upon restimulation, and are deficient in activation-induced cell death (AICD). Additionally, GADD45 gamma deficiencies caused reduced contact hypersensitivity in mice. Thus, GADD45 gamma mediates activation of the p38 and JNK pathways and effector function of T(H)1 cells.