GADD45γ mediates the activation of the p38 and JNK MAP kinase pathways and cytokine production in effector T_H1 cells

The p38 and JNK stress-activated MAPK signal transduction pathways are activated by T cell receptor (TCR) signaling and are required for IFN-γ production by T_H1 effector cells. Here, we show that the expression of GADD45γ is induced during T cell activation and that the level of expression is higher in T_H1 cells than in T_H2 cells. T_H1 cells from GADD45γ^-/- mice are severely compromised in their abilities to activate p38 and JNK in response to TCR signaling, produce much less IFN-γ upon restimulation, and are deficient in activation-induced cell death (AICD). Additionally, GADD45γ deficiencies caused reduced contact hypersensitivity in mice. Thus, GADD45γ mediates activation of the p38 and JNK pathways and effector function of T_H1 cells.