VISTA 是幼稚 T 细胞静止和外周耐受的检查点调节剂。
VISTA is a checkpoint regulator for naïve T cell quiescence and peripheral tolerance.
机构信息
Department of Microbiology and Immunology, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
出版信息
Science. 2020 Jan 17;367(6475). doi: 10.1126/science.aay0524.
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.
负性检查点调节剂（NCRs）调节 T 细胞对自身抗原的免疫反应，限制自身免疫的发展。与所有其他在激活的 T 淋巴细胞上表达的 NCR 不同，T 细胞活化的 V 型免疫球蛋白结构域抑制因子（VISTA）在幼稚 T 细胞上表达。我们报告了小鼠幼稚 T 细胞区室中一种出乎意料的异质性，其中 VISTA 的缺失破坏了主要的静止幼稚 T 细胞亚群并增强了自身反应性。激动性 VISTA 结合通过促进抗原诱导的外周 T 细胞删除来增加 T 细胞耐受性。尽管 VISTA 是幼稚 T 细胞稳态的关键参与者，但在炎症条件下，它抑制幼稚 T 细胞反应的能力丧失。因此，VISTA 是幼稚 T 细胞的一种独特的 NCR，对于静止和外周耐受的稳态维持至关重要。
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