Journal
SCIENCE
Volume 367, Issue 6475, Pages 264-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aay0524
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Funding
- NIH [R01AR070760, R01CA214062, 1R21CA227996-01A1, RR180061, R01HL56067, R01 HL11879, R37A134495]
- Cancer Prevention and Research institute of Texas [RR180061]
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Negative checkpoint regulators (NCRs) temper the T cell immune response to self-antigens and limit the development of autoimmunity. Unlike all other NCRs that are expressed on activated T lymphocytes, V-type immunoglobulin domain-containing suppressor of T cell activation (VISTA) is expressed on naive T cells, We report an unexpected heterogeneity within the naive I cell compartment in mice, where loss of VISTA disrupted the major quiescent naive T cell subset and enhanced self-reactivity, Agonistic VISTA engagement increased T cell tolerance by promoting antigen-induced peripheral T cell deletion Although a critical player in naive T cell homeostasis, the ability of VISTA to restrain naive T cell responses was lost under inflammatory conditions. VISTA is therefore a distinctive NCR of naive T cells that is critical for steady-state maintenance of quiescence and peripheral tolerance
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