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CD160 Plays a Protective Role During Chronic Infection by Enhancing Both Functionalities and Proliferative Capacity of CD8+ T Cells
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CD160 Plays a Protective Role During Chronic Infection by Enhancing Both Functionalities and Proliferative Capacity of CD8+ T Cells
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Journal Article
CD160 Plays a Protective Role During Chronic Infection by Enhancing Both Functionalities and Proliferative Capacity of CD8+ T Cells
2020
Overview
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 a cross-sectional study and in a 60-month longitudinal cohort, displaying 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. The 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.
Publisher
Frontiers Media SA,Frontiers Media S.A
Subject
1-Phosphatidylinositol 3-kinase
/ Acquired immune deficiency syndrome
/ AIDS
/ Animals
/ CD160
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - transplantation
/ Cloning
/ Costimulatory and Inhibitory T-Cell Receptors - immunology
/ Female
/ Gene Products, gag - physiology
/ GPI-Linked Proteins - deficiency
/ GPI-Linked Proteins - immunology
/ HIV
/ HIV-1
/ Human immunodeficiency virus
/ Humans
/ Lymphocytic Choriomeningitis - immunology
/ Male
/ Mice
/ Peptides
/ Receptors, Immunologic - deficiency
/ Receptors, Immunologic - immunology
/ Software
/ T cell
/ T-Lymphocyte Subsets - immunology
