2. Academic Validation
  3. VISTA is a checkpoint regulator for naïve T cell quiescence and peripheral tolerance

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

  • Science. 2020 Jan 17;367(6475):eaay0524. doi: 10.1126/science.aay0524.
Mohamed A ElTanbouly # 1,  Yanding Zhao # 2 3,  Elizabeth Nowak 1,  Jiannan Li 4,  Evelien Schaafsma 2 3,  Isabelle Le Mercier 5,  Sabrina Ceeraz 6,  J Louise Lines 1,  Changwei Peng 7 8,  Catherine Carriere 9,  Xin Huang 9,  Maria Day 9,  Brent Koehn 10,  Sam W Lee 11,  Milagros Silva Morales 7,  Kristin A Hogquist 7 8,  Stephen C Jameson 7 8,  Daniel Mueller 7 8,  Jay Rothstein 9,  Bruce R Blazar 10 12,  Chao Cheng 13 14,  Randolph J Noelle 15 9
Affiliations

Affiliations

  • 1 Department of Microbiology and Immunology, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
  • 2 Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
  • 3 Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
  • 4 Adimab LLC, Lebanon, NH, USA.
  • 5 KSQ Therapeutics, Cambridge, MA, USA.
  • 6 Immunology Discovery, Janssen Research and Development LLC, Spring House, PA, USA.
  • 7 Division of Rheumatic and Autoimmune Diseases, Center for Immunology, University of Minnesota, Minneapolis, MN, USA.
  • 8 The Center for Immunology, University of Minnesota, Minneapolis, MN, USA.
  • 9 ImmuNext Corporation, Lebanon, NH, USA.
  • 10 Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
  • 11 Yale University School of Medicine, New Haven, CT, USA.
  • 12 Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
  • 13 Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hanover, NH, USA. [email protected] [email protected].
  • 14 Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
  • 15 Department of Microbiology and Immunology, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA. [email protected] [email protected].
  • # Contributed equally.
PMID: 31949051 DOI: 10.1126/science.aay0524
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.

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