Re-defining t-cell exhaustion: Subset, function, and regulation

Se Jin Im, Sang Jun Ha

Research output: Contribution to journalReview articlepeer-review

25 Citations (Scopus)


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.

Original languageEnglish
Article numbere2
JournalImmune Network
Issue number1
Publication statusPublished - 2020 Feb

Bibliographical note

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).

Publisher Copyright:
© 2020. The Korean Association of Immunologists.

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases


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