JNK2 Is Required for Efficient T-cell Activation and Apoptosis but Not for Normal Lymphocyte Development

Curr Biol. 1999 Feb 11;9(3):116-25. doi: 10.1016/s0960-9822(99)80065-7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Apoptosis*
  • B-Lymphocytes / immunology
  • Dexamethasone / pharmacology
  • Drug Resistance
  • Gene Targeting
  • Isoenzymes / deficiency
  • Isoenzymes / genetics
  • Isoenzymes / physiology*
  • Lymphocyte Activation* / drug effects
  • Lymphocyte Activation* / radiation effects
  • Mice
  • Mice, Knockout
  • Mitogen-Activated Protein Kinase 9
  • Mitogen-Activated Protein Kinases*
  • Muromonab-CD3 / pharmacology
  • Protein Kinases / deficiency
  • Protein Kinases / genetics
  • Protein Kinases / physiology*
  • RNA Splicing
  • T-Lymphocytes / cytology
  • T-Lymphocytes / enzymology*
  • T-Lymphocytes / immunology
  • Ultraviolet Rays
  • fas Receptor / immunology

Substances

  • Antibodies, Monoclonal
  • Isoenzymes
  • Muromonab-CD3
  • fas Receptor
  • Dexamethasone
  • Protein Kinases
  • Mitogen-Activated Protein Kinase 9
  • Mitogen-Activated Protein Kinases