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

Immune Network 2020년 20권 1호 p.2 ~ 2
 ( Im Se-Jin ) - Sungkyunkwan University School of Medicine Department of Immunology

하상준 ( Ha Sang-Jun ) - Yonsei University College of Life Science and Biotechnology Department of Biochemistry

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.

키워드

T-cell exhaustion; PD-1; Immunotherapy; Stem cell-like CD8 T-cell subset
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