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Science. 2020 Jan 17;367(6475). pii: eaay0524. doi: 10.1126/science.aay0524.

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

Author information

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. rjn@dartmouth.edu chao.cheng@bcm.edu.
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. rjn@dartmouth.edu chao.cheng@bcm.edu.
#
Contributed equally

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.

Comment in

PMID:
31949051
DOI:
10.1126/science.aay0524

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