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T cell exhaustion

Nature Immunology volume 12, pages 492–499 (2011)Cite this article

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Abstract

T cell exhaustion is a state of T cell dysfunction that arises during many chronic infections and cancer. It is defined by poor effector function, sustained expression of inhibitory receptors and a transcriptional state distinct from that of functional effector or memory T cells. Exhaustion prevents optimal control of infection and tumors. Recently, a clearer picture of the functional and phenotypic profile of exhausted T cells has emerged and T cell exhaustion has been defined in many experimental and clinical settings. Although the pathways involved remain to be fully defined, advances in the molecular delineation of T cell exhaustion are clarifying the underlying causes of this state of differentiation and also suggest promising therapeutic opportunities.

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Figure 1: Hierarchical T cell exhaustion during chronic infection.
Figure 2: Subsets of exhausted T cells and combinatorial strategies to reverse exhaustion.

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Acknowledgements

I thank the members of my laboratory and N. Haining for discussions. Supported by the US National Institutes of Health (AI071309, AI083022, AI082630, HHSN226200500030), the Commonwealth of Pennsylvania, the Ellison Medical Foundation and the Dana Foundation.

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  1. Department of Microbiology, Institute for Immunology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA

    E John Wherry

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E.J.W. has a patent licensing agreement for the PD-1 pathway.

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Wherry, E. T cell exhaustion. Nat Immunol 12, 492–499 (2011). https://doi.org/10.1038/ni.2035

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