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Seminars in Immunopathology

, Volume 41, Issue 3, pp 327–337 | Cite as

CD8+ T cell exhaustion

  • Makoto KurachiEmail author
Review

Abstract

CD8+ T cells are important for the protective immunity against intracellular pathogens and tumor. In the case of chronic infection or cancer, CD8+ T cells are exposed to persistent antigen and/or inflammatory signals. This excessive amount of signals often leads CD8+ T cells to gradual deterioration of T cell function, a state called “exhaustion.” Exhausted T cells are characterized by progressive loss of effector functions (cytokine production and killing function), expression of multiple inhibitory receptors (such as PD-1 and LAG3), dysregulated metabolism, poor memory recall response, and homeostatic proliferation. These altered functions are closely related with altered transcriptional program and epigenetic landscape that clearly distinguish exhausted T cells from normal effector and memory T cells. T cell exhaustion is often associated with inefficient control of persisting infections and cancers, but re-invigoration of exhausted T cells with inhibitory receptor blockade can promote improved immunity and disease outcome. Accumulating evidences support the therapeutic potential of targeting exhausted T cells. However, exhausted T cells comprise heterogenous cell population with distinct responsiveness to intervention. Understanding molecular mechanism of T cell exhaustion is essential to establish rational immunotherapeutic interventions.

Keywords

CD8 T cell Exhaustion Chronic infection Inhibitory receptor Cancer immunotherapy 

Notes

Acknowledgments

I would like to thank Junko Kurachi and John Wherry for technical assistance and helpful discussion. This work was supported by Chozen project (Kanazawa University).

Compliance with ethical standards

Conflict of interest

The author declares that he has no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Molecular Genetics, Graduate School of Medical SciencesKanazawa UniversityKanazawaJapan

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