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Trends Immunol. 2014 Feb;35(2):51-60. doi: 10.1016/j.it.2013.10.001. Epub 2013 Nov 6.

Tolerance and exhaustion: defining mechanisms of T cell dysfunction.

Author information

1
Department of Immunology, University of Washington, Seattle, WA 98109, USA; Program of Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Electronic address: aschieti@uw.edu.
2
Department of Immunology, University of Washington, Seattle, WA 98109, USA; Program of Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. Electronic address: pgreen@u.washington.edu.

Abstract

CD8 T cell activation and differentiation are tightly controlled, and dependent on the context in which naïve T cells encounter antigen, can either result in functional memory or T cell dysfunction, including exhaustion, tolerance, anergy, or senescence. With the identification of phenotypic and functional traits shared in different settings of T cell dysfunction, distinctions between such dysfunctional states have become blurred. Here, we discuss distinct states of CD8 T cell dysfunction, with an emphasis on: (i) T cell tolerance to self-antigens (self-tolerance); (ii) T cell exhaustion during chronic infections; and (iii) tumor-induced T cell dysfunction. We highlight recent findings on cellular and molecular characteristics defining these states, cell-intrinsic regulatory mechanisms that induce and maintain them, and strategies that can lead to their reversal.

KEYWORDS:

CD8 T cells; T cell differentiation; T cell dysfunction; chronic infection; exhaustion; self-tolerance; tumors

PMID:
24210163
PMCID:
PMC3946600
DOI:
10.1016/j.it.2013.10.001
[Indexed for MEDLINE]
Free PMC Article

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