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CD8+ T cell exhaustion

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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.

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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).

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  1. Department of Molecular Genetics, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8640, Japan

    Makoto Kurachi

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This article is a contribution to the special issue on The Pathogenicity of Acquired Immunity in Human Diseases - Guest Editor: Kiyoshi Hirahara

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Kurachi, M. CD8+ T cell exhaustion. Semin Immunopathol 41, 327–337 (2019). https://doi.org/10.1007/s00281-019-00744-5

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