GADD45 gamma mediates the activation of the p38 and JNK MAP kinase pathways and cytokine production in effector T(H)1 cells

The p38 and JNK stress-activated MAPK signal transduction pathways are acti vated by T cell receptor (TCR) signaling and are required for IFN-gamma pro duction by T(H)1 effector cells. Here, we show that the expression of GADD4 5 gamma is induced during T cell activation and that the level of expressio n 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 restimu lation, and are deficient in activation-induced cell death (AICD). Addition ally, GADD45 gamma deficiencies caused reduced contact hypersensitivity in mice. Thus, GADD45 gamma mediates activation of the p38 and JNK pathways an d effector function of T(H)1 cells.