JNK2 is required for efficient T-cell activation and apoptosis but not for normal lymphocyte development
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JNK2 is required for efficient T-cell activation and apoptosis but not for normal lymphocyte development. / Sabapathy, K; Hu, Y; Kallunki, T; Schreiber, M; David, J P; Jochum, W; Wagner, E F; Karin, M.
in: CURR BIOL, Jahrgang 9, Nr. 3, 11.02.1999, S. 116-25.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - JNK2 is required for efficient T-cell activation and apoptosis but not for normal lymphocyte development
AU - Sabapathy, K
AU - Hu, Y
AU - Kallunki, T
AU - Schreiber, M
AU - David, J P
AU - Jochum, W
AU - Wagner, E F
AU - Karin, M
PY - 1999/2/11
Y1 - 1999/2/11
N2 - BACKGROUND: The Jun N-terminal kinase (JNK) signaling pathway has been implicated in cell proliferation and apoptosis, but its function seems to depend 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 by antibody to the CD3 component of the T-cell receptor (TCR) complex - proliferation 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-induced peripheral T-cell apoptosis was comparable between mutant and wild-type mice, but immature (CD4(+) CD8(+)) thymocytes lacking JNK2 were resistant to apoptosis induced by administration of anti-CD3 antibody in vivo. The lack of JNK2 also resulted in partial resistance of thymocytes to anti-CD3 antibody in vitro, but had little or no effect on apoptosis induced by anti-Fas antibody, dexamethasone or ultraviolet-C (UVC) radiation.CONCLUSIONS: JNK2 is essential for efficient activation of peripheral T cells but not B cells. Peripheral T-cell activation is probably required indirectly for induction of thymocyte apoptosis resulting from administration of anti-CD3 antibody in vivo. JNK2 functions in a cell-type-specific and stimulus-dependent manner, being required for apoptosis of immature thymocytes induced by anti-CD3 antibody but not for apoptosis induced by anti-Fas antibody, UVC or dexamethasone. JNK2 is not required for activation-induced cell death of mature T cells.
AB - BACKGROUND: The Jun N-terminal kinase (JNK) signaling pathway has been implicated in cell proliferation and apoptosis, but its function seems to depend 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 by antibody to the CD3 component of the T-cell receptor (TCR) complex - proliferation 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-induced peripheral T-cell apoptosis was comparable between mutant and wild-type mice, but immature (CD4(+) CD8(+)) thymocytes lacking JNK2 were resistant to apoptosis induced by administration of anti-CD3 antibody in vivo. The lack of JNK2 also resulted in partial resistance of thymocytes to anti-CD3 antibody in vitro, but had little or no effect on apoptosis induced by anti-Fas antibody, dexamethasone or ultraviolet-C (UVC) radiation.CONCLUSIONS: JNK2 is essential for efficient activation of peripheral T cells but not B cells. Peripheral T-cell activation is probably required indirectly for induction of thymocyte apoptosis resulting from administration of anti-CD3 antibody in vivo. JNK2 functions in a cell-type-specific and stimulus-dependent manner, being required for apoptosis of immature thymocytes induced by anti-CD3 antibody but not for apoptosis induced by anti-Fas antibody, UVC or dexamethasone. JNK2 is not required for activation-induced cell death of mature T cells.
KW - Animals
KW - Antibodies, Monoclonal
KW - Antigens, CD95
KW - Apoptosis
KW - B-Lymphocytes
KW - Dexamethasone
KW - Drug Resistance
KW - Gene Targeting
KW - Isoenzymes
KW - Lymphocyte Activation
KW - Mice
KW - Mice, Knockout
KW - Mitogen-Activated Protein Kinase 9
KW - Mitogen-Activated Protein Kinases
KW - Muromonab-CD3
KW - Protein Kinases
KW - RNA Splicing
KW - T-Lymphocytes
KW - Ultraviolet Rays
M3 - SCORING: Journal article
C2 - 10021384
VL - 9
SP - 116
EP - 125
JO - CURR BIOL
JF - CURR BIOL
SN - 0960-9822
IS - 3
ER -