AUTHOR=Zhang Linxia , Zhang Anli , Xu Jun , Qiu Chao , Zhu Lingyan , Qiu Chenli , Fu Weihui , Wang Ying , Ye Lilin , Fu Yang-xin , Zhao Chen , Zhang Xiaoyan , Xu Jianqing 

TITLE=CD160 Plays a Protective Role During Chronic Infection by Enhancing Both Functionalities and Proliferative Capacity of CD8+ T Cells

JOURNAL=Frontiers in Immunology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.02188

DOI=10.3389/fimmu.2020.02188

ISSN=1664-3224

ABSTRACT=The understanding of protective immunity during HIV infection remains elusive. Here we showed that CD160 defines a polyfunctional and proliferative CD8+ T cell subset with a protective role during chronic HIV-1 infection. CD160+CD8+ T cells derived from HIV+ patients correlated with slow progressions both in cross-sectional study and in a 36-month longitudinal cohort, displayed enhanced cytotoxicity and proliferative capacity in response to HIV Gag stimulation; triggering CD160 promoted their functionalities through MEK-ERK and PI3K-AKT pathways. These observations were corroborated by studying chronic lymphocytic choriomeningitis virus (LCMV) infection in mice. Genetic ablation of CD160 severely impaired LCMV-specific CD8+ T cell functionalities and thereby resulted in loss of virus control. Interestingly, transcriptional profiling showed multiple costimulatory and survival pathways likely to be involved in CD160+ T cell development. Our data demonstrated that CD160 acts as a costimulatory molecule positively regulating CD8+ T cells during chronic viral infections, thus representing a potential target for immune intervention.