JNK2 negatively regulates CD8+ T cell effector function and anti-tumor immune response
JNK2 negatively regulates CD8+ T cell effector function and anti-tumor immune response
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DOI：
10.1002/eji.200636726
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发表时间：
2007-03-01
影响因子：
5.4
通讯作者：
Yin, Zhinan
中科院分区：
文献类型：
--
作者：
Tao, Jian;Gao, Yunfei;Yin, Zhinan
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.
