TY - JOUR
T1 - CD160 Signaling Is Essential for CD8+ T Cell Memory Formation via Upregulation of 4-1BB
AU - Zhang, Linxia
AU - Zhang, Anli
AU - Zhu, Xinyu
AU - Tian, Xinmei
AU - Guo, Jiaohan
AU - He, Qian
AU - Zhu, Lingyan
AU - Yuan, Songhua
AU - Zhao, Chen
AU - Zhang, Xiaoyan
AU - Xu, Jianqing
N1 - Publisher Copyright:
© 2023 by The American Association of Immunologists, Inc.
PY - 2023/11/1
Y1 - 2023/11/1
N2 - A better understanding of the regulatory mechanisms governing the development of memory CD8+ T cells could provide instructive insights into vaccination strategies and T cell_based immunotherapies. In this article, we showed that CD160 surface protein is required for CD8+ T cell memory formation. In the response to acute lymphocytic choriomeningitis virus infection in a mouse model, CD160 ablation resulted in the failure of the development of all three memory CD8+ T cell subsets (central, effective, and tissue-resident memory), concomitant with a skewed differentiation into short-lived effector T cells. Such memoryrelated defect was manifested by a diminished protection from viral rechallenge. Mechanistically, CD160 deficiency led to downregulation of 4-1BB in activated CD8+ T cells, which contributes to the impaired cell survival and decreased respiratory capacity. The nexus between CD160 and 4-1BB was substantiated by the observation that ectopic introduction of 4-1BB was able to largely complement the loss of CD160 in memory CD8+ T cell development. Collectively, our studies discovered that CD160, once thought to be a coinhibitor of T cell signaling, is an essential promoter of memory CD8+ T cell development via activation of the costimulatory molecule 4-1BB.
AB - A better understanding of the regulatory mechanisms governing the development of memory CD8+ T cells could provide instructive insights into vaccination strategies and T cell_based immunotherapies. In this article, we showed that CD160 surface protein is required for CD8+ T cell memory formation. In the response to acute lymphocytic choriomeningitis virus infection in a mouse model, CD160 ablation resulted in the failure of the development of all three memory CD8+ T cell subsets (central, effective, and tissue-resident memory), concomitant with a skewed differentiation into short-lived effector T cells. Such memoryrelated defect was manifested by a diminished protection from viral rechallenge. Mechanistically, CD160 deficiency led to downregulation of 4-1BB in activated CD8+ T cells, which contributes to the impaired cell survival and decreased respiratory capacity. The nexus between CD160 and 4-1BB was substantiated by the observation that ectopic introduction of 4-1BB was able to largely complement the loss of CD160 in memory CD8+ T cell development. Collectively, our studies discovered that CD160, once thought to be a coinhibitor of T cell signaling, is an essential promoter of memory CD8+ T cell development via activation of the costimulatory molecule 4-1BB.
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U2 - 10.4049/jimmunol.2200792
DO - 10.4049/jimmunol.2200792
M3 - Article
C2 - 37695685
AN - SCOPUS:85176566429
SN - 0022-1767
VL - 211
SP - 1367
EP - 1375
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -