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

• DOI: 10.1126/science.aay0524
• Publication Date: 2020-01-17T00:09:20Z
• Authors: Mohamed A. ElTanb...; 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 Mo...; Kristin A. Hogquist; Stephen C. Jameson; Daniel Mueller; Jay Rothstein; Bruce R. Blazar; Chao Cheng; Randolph J. Noelle
• Keywords: Peripheral tolerance

Negative checkpoint regulators (NCRs) temper the T cell immune response to self-antigens and limit development of autoimmunity. Unlike all other NCRs that are expressed on activated lymphocytes, V-type immunoglobulin domain-containing suppressor activation (VISTA) is naïve cells. We report an unexpected heterogeneity within compartment in mice, where loss VISTA disrupted major quiescent subset enhanced self-reactivity. Agonistic engagement increased tolerance by promoting antigen-induced peripheral deletion. Although a critical player homeostasis, ability restrain responses was lost under inflammatory conditions. therefore distinctive NCR cells for steady-state maintenance quiescence tolerance.