TRAF2 regulates T cell immunity by maintaining a Tpl2-ERK survival signaling axis in effector and memory CD8 T cells |
| |
| Authors: | Xiaoping Xie Lele Zhu Zuliang Jie Yanchuan Li Meidi Gu Xiaofei Zhou Hui Wang Jae-Hoon Chang Chun-Jung Ko Xuhong Cheng Shao-Cong Sun |
| |
| Affiliation: | 1.Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, Box 902, Houston, TX 77030 USA ;2.Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004 Jiangsu China ;3.College of Pharmacy, Yeungnam University, Gyeongsan, 712-749 Republic of Korea ;4.MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences, Houston, TX 77030 USA |
| |
| Abstract: | Generation and maintenance of antigen-specific effector and memory T cells are central events in immune responses against infections. We show that TNF receptor-associated factor 2 (TRAF2) maintains a survival signaling axis in effector and memory CD8 T cells required for immune responses against infections. This signaling axis involves activation of Tpl2 and its downstream kinase ERK by NF-κB-inducing kinase (NIK) and degradation of the proapoptotic factor Bim. NIK mediates Tpl2 activation by stimulating the phosphorylation and degradation of the Tpl2 inhibitor p105. Interestingly, while NIK is required for Tpl2-ERK signaling under normal conditions, uncontrolled NIK activation due to loss of its negative regulator, TRAF2, causes constitutive degradation of p105 and Tpl2, leading to severe defects in ERK activation and effector/memory CD8 T cell survival. Thus, TRAF2 controls a previously unappreciated signaling axis mediating effector/memory CD8 T cell survival and protective immunity. |
| |
| Keywords: | T cell survival Effector and memory CD8 T cells Protective immunity Bacterial infection TRAF2 NIK Tpl2 |
|
|
