Re-defining T-Cell Exhaustion: Subset, Function, and Regulation
- Author:
Se Jin IM
1
;
Sang Jun HA
Author Information
- Publication Type:Review
- Keywords: T-cell exhaustion; PD-1; Immunotherapy; Stem cell-like CD8 T-cell subset
- MeSH: Animals; Humans; Immunotherapy; Lymphocytic choriomeningitis virus; Memory; Mice; Stem Cells; T-Lymphocyte Subsets; T-Lymphocytes; Vaccination
- From:Immune Network 2020;20(1):2-
- CountryRepublic of Korea
- Language:English
- 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.
