Tolerance and exhaustion: defining mechanisms of T cell dysfunction.

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  • Additional Information
    • Source:
      Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 100966032 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1471-4981 (Electronic) Linking ISSN: 14714906 NLM ISO Abbreviation: Trends Immunol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Oxford, UK : Elsevier Science Ltd., c2001-
    • Subject Terms:
      Immune Tolerance*/genetics; CD8-Positive T-Lymphocytes/*immunology; Animals ; CD8-Positive T-Lymphocytes/cytology ; Cell Differentiation/immunology ; Clonal Anergy ; Epigenesis, Genetic ; Humans ; Immunologic Memory ; Infections/immunology ; Lymphocyte Activation ; Mice ; Neoplasms/immunology ; Self Tolerance
    • 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.
      (Copyright © 2013 Elsevier Ltd. All rights reserved.)
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    • Grant Information:
      K99 CA172371 United States CA NCI NIH HHS; P01 CA018029 United States CA NCI NIH HHS; R01 CA033084 United States CA NCI NIH HHS; R21 AI107776 United States AI NIAID NIH HHS
    • Contributed Indexing:
      Keywords: CD8 T cells; T cell differentiation; T cell dysfunction; chronic infection; exhaustion; self-tolerance; tumors
    • Publication Date:
      Date Created: 20131112 Date Completed: 20140813 Latest Revision: 20231120
    • Publication Date:
      20240829
    • Accession Number:
      PMC3946600
    • Accession Number:
      10.1016/j.it.2013.10.001
    • Accession Number:
      24210163