JNK2 negatively regulates CD8+ T cell effector function and anti-tumor immune response.
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.
Tao
Jian
J
Section of Rheumatology, Department of Medicine, Yale School of Medicine, New Haven, CT 06520-8031, USA.
Gao
Yunfei
Y
Li
Ming O
MO
He
Weifeng
W
Chen
Liang
L
Harvev
Bohdan
B
Davis
Roger J
RJ
Flavell
Richard A
RA
Yin
Zhinan
Z
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D015536:Down-Regulation / Q000276:immunology; D006131:Growth Inhibitors / Q000502:physiology; D008546:Melanoma, Experimental / Q000201:enzymology* / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D048056:Mitogen-Activated Protein Kinase 9 / Q000502:physiology*
D006131:Growth Inhibitors; D048056:Mitogen-Activated Protein Kinase 9