JNK2 negatively regulates CD8+ T cell effector function and anti-tumor immune response

Eur J Immunol. 2007 Mar;37(3):818-29. doi: 10.1002/eji.200636726.


JNK1 and JNK2 have distinct effects on activation, differentiation and function of CD8+ T cells. Our early studies demonstrated that JNK1 is required for CD8+ T cell-mediated tumor immune surveillance. However, the role of JNK2 in CD8+ T cell response and effector functions, especially in anti-tumor immune response, is unknown. To define the role of JNK2 in antigen-specific immune response, we have investigated CD8+ T cells from OT-1 CD8+ transgenic mice in response to either high- or low-affinity peptides. JNK2-/- CD8+ T cells proliferated better in response to both peptides, with more cell division and less cell death. In addition, JNK2-/- CD8+ T cells produced higher levels of IFN-gamma, which is associated with increased expression of T-bet and Eomesodermin (Eomes). Moreover, JNK2-/- CD8+ T cells expresses high levels of granzyme B and show increased CTL activity. Finally, the enhanced expansion and effector function of JNK2-/- CD8+ T cells was further evidenced by their capacity to delay tumor growth in vivo. In summary, our results demonstrate that JNK2 negatively regulates antigen-specific CD8+ T cell expansion and effector function, and thus selectively blocking JNK2 in CD8+ T cells may potentially enhance anti-tumor immune response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / enzymology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Line, Tumor
  • Cell Survival / immunology
  • Cytotoxicity Tests, Immunologic
  • Down-Regulation / immunology
  • Growth Inhibitors / physiology
  • Melanoma, Experimental / enzymology*
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / prevention & control*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinase 9 / physiology*


  • Growth Inhibitors
  • Mitogen-Activated Protein Kinase 9