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题名:JNK2 negatively regulates CD8+ T cell effector function and anti-tumor immune response.
作者:Tao J, Gao Y, Li MO, He W, Chen L, Harvev B, Davis RJ, Flavell RA, Yin Z. Related Articles, Links
来源:Eur J Immunol[IF=4.876]. 2007 Mar;37(3):818-29.
URL :http://dx.doi.org/10.1002/eji.200636726
日期:070415
摘要: Jian Tao 1, Yunfei Gao 1 4, Ming O. Li 2, Weifeng He 1 5, Liang Chen 1 6, Bohdan Harvev 1, Roger J. Davis 3, Richard A. Flavell 2, Zhinan Yin 1 *

1Section of Rheumatology, Department of Medicine, Yale School of Medicine, New Haven, CT, USA
2Section of Immunobiology, Yale School of Medicine, New Haven, CT, USA
3University of Massauchusetts Medical School, Morcester, MA, USA
4Department of Immunology, University of Toronto, Toronto, Canada
5State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University, Chongging, 400038, PR China
6Department of Medical Oncology, Dana-Farber Cancer Institute, MA, USA

email: Zhinan Yin (zhinan.yin@yale.edu)

*Correspondence to Zhinan Yin, Section of Rheumatology, Yale School of Medicine, Box 208031, TAC building Room 517, 300 Cedar Street, New Haven, CT 06520-8031, USA, Fax: +1-203-785-7053

Funded by:
Arthritis Foundation Investigator Award
NIH, NIAMS - K01 AR 02188
NIH - R01AI56219

Keywords
Cell activation ?Cell differentiation ?CTL ?IFN- ?Signal transduction

Abstract

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-, 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. 14:

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