TRAF2 regulates T cell immunity by maintaining a Tpl2-ERK survival signaling axis in effector and memory CD8 T cells

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 inf...

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Bibliographic Details
Published in:Cellular & molecular immunology 2021-09, Vol.18 (9), p.2262-2274
Main Authors: Xie, Xiaoping, Zhu, Lele, Jie, Zuliang, Li, Yanchuan, Gu, Meidi, Zhou, Xiaofei, Wang, Hui, Chang, Jae-Hoon, Ko, Chun-Jung, Cheng, Xuhong, Sun, Shao-Cong
Format: Article
Language:English
Subjects:
631/250/2152/1566/1618
631/250/516
Antibodies
Apoptosis
Biomedical and Life Sciences
Biomedicine
CD8 antigen
CD8-Positive T-Lymphocytes - metabolism
Cell survival
Degradation
Effector cells
Extracellular signal-regulated kinase
Immunity
Immunological memory
Immunology
Lymphocytes
Lymphocytes T
Medical Microbiology
Memory cells
Microbiology
NF-kappa B - metabolism
NF-κB protein
Phosphorylation
Signal Transduction
TNF Receptor-Associated Factor 2 - metabolism
TRAF2 protein
Tumor necrosis factor
Tumor necrosis factor receptors
Vaccine
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Summary: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.
ISSN:1672-7681
2042-0226
DOI:10.1038/s41423-020-00583-7