title: Tolerance and exhaustion: defining mechanisms of T cell dysfunction.
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.
authors.affiliation: 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.
authors.forename: Andrea
authors.initials: A
authors.lastname: Schietinger
authors.affiliation: 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.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Greenberg
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D017635:Clonal Anergy; D044127:Epigenesis, Genetic; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D007156:Immunologic Memory; D007239:Infections / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D009369:Neoplasms / Q000276:immunology; D017634:Self Tolerance
keywords: CD8 T cells; T cell differentiation; T cell dysfunction; chronic infection; exhaustion; self-tolerance; tumors