VISTA is a checkpoint regulator for naïve T cell quiescence and peripheral tolerance
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 naï...
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Published in | Science (American Association for the Advancement of Science) Vol. 367; no. 6475 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
The American Association for the Advancement of Science
17.01.2020
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Subjects | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author contributions: Conceptualization: R.J.N and M.A.E.; Methodology: R.J.N., M.A.E., and Y.Z.; Investigation: M.A.E., Y.Z., E.N., E.S., J.L.L., B.K., I.L., C.C., X.H., S.C.J., K.A.H., C.P., and M.S.M.; Writing – review & editing: R.J.N., M.A.E., D.M., S.C.J.,Y.Z., B.R.B., and C.C.; Resources: R.J.N and C.C.; Supervision: R.J.N. These authors contributed equally to this work. |
ISSN: | 0036-8075 1095-9203 |
DOI: | 10.1126/science.aay0524 |