小柯机器人

美国达特茅斯盖塞尔医学院Randolph J. Noelle、Chao Cheng等研究人员合作发现，VISTA是初始T细胞静止和外周耐受的检查点调节因子。相关论文发表在2020年1月17日出版的《科学》上。

据研究人员介绍，负检查点调节因子（NCR）调控T细胞对自身抗原的免疫反应并限制自身免疫的发展。与在活化T淋巴细胞上表达的所有其他NCR不同，在初始T细胞上表达含V型免疫球蛋白结构域的T细胞活化抑制因子（VISTA）。

研究人员报道了小鼠初始的T细胞区室中的异质性，其中VISTA的丧失破坏了主要的静态初始T细胞亚群并增强了自身反应性。激动性VISTA参与通过促进抗原诱导的外周T细胞缺失而增加了T细胞耐受性。尽管在初始T细胞稳态中起关键作用，但在炎症条件下，VISTA抑制初始T细胞反应的能力丧失了。因此，VISTA是初始T细胞的独特NCR，对于稳定维持静止状态和外周耐受至关重要。

附：英文原文

Title: VISTA is a checkpoint regulator for nave T cell quiescence and peripheral tolerance

Author: Mohamed A. ElTanbouly, 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 Morales, Kristin A. Hogquist, Stephen C. Jameson, Daniel Mueller, Jay Rothstein, Bruce R. Blazar, Chao Cheng, Randolph J. Noelle

Issue&Volume: 2020/01/17

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

DOI: 10.1126/science.aay0524

Source: https://science.sciencemag.org/content/367/6475/eaay0524