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

被引：201

作者：

ElTanbouly, Mohamed A. ^{[1
]}

Zhao, Yanding ^{[2
,3
]}

Nowak, Elizabeth ^{[1
]}

Li, Jiannan ^{[4
]}

Schaafsma, Evelien ^{[2
,3
]}

Le Mercier, Isabelle ^{[5
]}

Ceeraz, Sabrina ^{[6
]}

Lines, J. Louise ^{[1
]}

Peng, Changwei ^{[7
,8
]}

Carriere, Catherine ^{[9
]}

Huang, Xin ^{[9
]}

Day, Maria ^{[9
]}

Koehn, Brent ^{[10
]}

Lee, Sam W. ^{[11
]}

Morales, Milagros Silva ^{[7
]}

Hogquist, Kristin A. ^{[7
,8
]}

Jameson, Stephen C. ^{[7
,8
]}

Mueller, Daniel ^{[7
,8
]}

Rothstein, Jay ^{[9
]}

Blazar, Bruce R. ^{[10
,12
]}

Cheng, Chao ^{[3
,13
]}

Noelle, Randolph J. ^{[1
,9
]}

机构：

[1] Geisel Sch Med Dartmouth, Norris Cotton Canc Ctr, Dept Microbiol & Immunol, Lebanon, NH 03756 USA

[2] Geisel Sch Med Dartmouth, Dept Mol & Syst Biol, Lebanon, NH 03756 USA

[3] Geisel Sch Med Dartmouth, Dept Biomed Data Sci, Lebanon, NH 03756 USA

[4] Adimab LLC, Lebanon, NH USA

[5] KSQ Therapeut, Cambridge, MA USA

[6] Janssen Res & Dev LLC, Immunol Discovery, Spring House, PA USA

[7] Univ Minnesota, Ctr Immunol, Div Rheumat & Autoimmune Dis, Minneapolis, MN USA

[8] Univ Minnesota, Ctr Immunol, Minneapolis, MN USA

[9] ImmuNext Corp, Lebanon, NH USA

[10] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA

[11] Yale Univ, Sch Med, New Haven, CT USA

[12] Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA

[13] Baylor Coll Med, Dept Med, Houston, TX 77030 USA

来源：

SCIENCE | 2020年 / 367卷 / 6475期

关键词：

VERSUS-HOST-DISEASE; MOLECULAR-MECHANISMS; MONOCLONAL-ANTIBODY; APOPTOTIC CELLS; UP-REGULATION; MURINE LUPUS; DIFFERENTIATION; MOUSE; MICE; GENE;

D O I：

10.1126/science.aay0524

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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

引用

页码：264 / +

页数：49

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