Journal
TRENDS IN IMMUNOLOGY
Volume 35, Issue 2, Pages 51-60Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.it.2013.10.001
Keywords
CDS T cells; T cell differentiation; T cell dysfunction; self-tolerance; exhaustion; chronic infection; tumors
Categories
Funding
- National Institutes of Health [R01 CA033084, R21 AI107776, K99 CA172371]
- Stand Up To Cancer-Cancer Research Institute Cancer Immunology Translational Cancer Research Grant
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CD8 T cell activation and differentiation are tightly controlled, and dependent on the context in which naive 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 (selftolerance); (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.
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