JNK2 is required for efficient T-cell activation and apoptosis but not fornormal lymphocyte development

Background: The Jun N-terminal kinase (JNK) signaling pathway has been impl icated in cell proliferation and apoptosis, but its function seems to depen d on the cell type and inducing signal. In T cells, JNK has been implicated in both antigen-induced activation and apoptosis. Results: We generated mice lacking the JNK2 isozymes. The mutant mice were healthy and fertile but defective in peripheral T-cell activation induced b y antibody to the CD3 component of the T-cell receptor (TCR) complex prolif eration and production of interleukin-2 (IL-2), IL-4 and interferon-gamma ( IFN-gamma) were reduced. The proliferation defect was restored by exogenous IL-2. B-cell activation was normal in the absence of JNK2. Activation-indu ced peripheral T-cell apoptosis was comparable between mutant and wild-type mice, but immature (CD4(+)CD8(+)) thymocytes lacking JNK2 were resistant t o apoptosis induced by administration of anti-CD3 antibody in vivo. The lac k of JNK2 also resulted in partial resistance of thymocytes to anti-CDS ant ibody in vitro, but had little or no effect on apoptosis induced by anti-fa s antibody, dexamethasone or ultraviolet-C (UVC) radiation. Conclusions: JNK2 is essential for efficient activation of peripheral T cel ls but not B cells. Peripheral T-cell activation is probably required indir ectly for induction of thymocyte apoptosis resulting from administration of anti-CD3 antibody in vivo. JNK2 functions in a cell-type-specific and stim ulus-dependent manner, being required for apoptosis of immature thymocytes induced by anti-CD3 antibody but not for apoptosis induced by anti-fas anti body, UVC or dexamethasone. JNK2 is not required for activation-induced cel l death of mature T cells.