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

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4 Scopus citations

Abstract

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
JournalScience
Volume367
Issue number6475
DOIs
StatePublished - Jan 17 2020

PubMed: MeSH publication types

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

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    ElTanbouly, M. A., Zhao, Y., Nowak, E., Li, J., Schaafsma, E., Le Mercier, I., Ceeraz, S., Lines, J. L., Peng, C., Carriere, C., Huang, X., Day, M., Koehn, B., Lee, S. W., Morales, M. S., Hogquist, K. A., Jameson, S. C., Mueller, D., Rothstein, J., ... Noelle, R. J. (2020). VISTA is a checkpoint regulator for naïve T cell quiescence and peripheral tolerance. Science, 367(6475), [eaay0524]. https://doi.org/10.1126/science.aay0524