VISTA is a checkpoint regulator for naïve T cell quiescence and peripheral tolerance

Mohamed A. ElTanbouly, Yanding Zhao, Elizabeth Nowak, Jiannan Li, Evelien Schaafsma, Isabelle Le Mercier, Sabrina Ceeraz, J. Louise Lines, Changwei Peng, Catherine Carriere, Xin Huang, Maria Day, Brent Koehn, Sam W. Lee, Milagros Silva Morales, Kristin A. Hogquist, Stephen C. Jameson, Daniel Mueller, Jay Rothstein, Bruce R. BlazarChao Cheng, Randolph J. Noelle

Research output: Contribution to journalArticlepeer-review

93 Scopus citations


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 naïve T cells. We report an unexpected heterogeneity within the naïve T cell compartment in mice, where loss of VISTA disrupted the major quiescent naïve 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 naïve T cell homeostasis, the ability of VISTA to restrain naïve T cell responses was lost under inflammatory conditions. VISTA is therefore a distinctive NCR of naïve T cells that is critical for steady-state maintenance of quiescence and peripheral tolerance.

Original languageEnglish (US)
Article numbereaay0524
Issue number6475
StatePublished - Jan 17 2020

Bibliographical note

Funding Information:
Research was supported by NIH grants R01AR070760 (R.J.N.), R01CA214062 (R.J.N.), 1R21CA227996-01A1 (C.C.), RR180061 (C.C.), R01 HL56067 (B.R.B.), R01 HL 11879 (B.R.B.), and R37 AI34495 (B.R.B.) and Cancer Prevention and Research institute of Texas grant RR180061 (C.C.).

Publisher Copyright:
Copyright © 2020 The Authors,

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


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