Re-defining T-Cell Exhaustion: Subset, Function, and Regulation

• Type of Material: Article
• Authors: Sejin Im, Emory University; Sang Ha, Emory University
• Language: English
• Date: 2020-02-01
• Publisher: Korean Association of Immunologists (KAI)
• Publication Version: Final Published Version
• Copyright Statement: © 2020. The Korean Association of Immunologists.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.4110/in.2020.20.e2
• Title of Journal or Parent Work: Immune Network
• Volume: 20
• Issue: 1
• Start Page: e2
• End Page: e2
• Grant/Funding Information: This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2017R1A5A1014560, 2018R1A2A1A05076997, 2018M3A9H3024850, 2019M3A9B6065221).
• Keywords: Life Sciences & Biomedicine; Immunotherapy; Driven differentiation; Inhibitory receptors; T-cell exhaustion; Immunology; PD-1 expression; Dysfunction; Science & Technology; Chronic infection; Dendritic cells; Antigen; UP-regulation; Lymphocytes; PD-1; Stem cell-like CD8 T-cell subset; Expansion
• Research Categories: Health Sciences, Immunology; Biology, Cell; Biology, Microbiology

Abstract

Acute viral infection or vaccination generates highly functional memory CD8 T cells following the Ag resolution. In contrast, persistent antigenic stimulation in chronic viral infection and cancer leads to a state of T-cell dysfunction termed T-cell exhaustion. We and other have recently identified a novel subset of exhausted CD8 T cells that act as stem cells for maintaining virus-specific CD8 T cells in a mouse model of chronic lymphocytic choriomeningitis virus infection. This stem cell-like CD8 T-cell subset has been also observed in both mouse and human tumor models. Most importantly, in both chronic viral infection and tumor models, the proliferative burst of Ag-specific CD8 T cells driven by PD-1-directed immunotherapy comes exclusively from this stem cell-like CD8 T-cell subset. Therefore, a better understanding of the mechanisms how CD8 T-cell subsets are regulated during chronic viral infection and cancer is required to improve the current immunotherapies that restore the function of exhausted CD8 T cells. In this review, we discuss the differentiation of virus-specific CD8 T cells during chronic viral infection, the characteristics and function of CD8 T-cell subsets, and the therapeutic intervention of PD-1-directed immunotherapy in cancer.