VISTA is a checkpoint regulator for naive T cell quiescence and peripheral tolerance
VISTA is a checkpoint regulator for naive T cell quiescence and peripheral tolerance
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DOI：
10.1126/science.aay0524
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发表时间：
2020-01-17
期刊：
影响因子：
56.9
通讯作者：
Noelle, Randolph J.
中科院分区：
文献类型：
--
作者：
ElTanbouly, Mohamed A.;Zhao, Yanding;Noelle, Randolph J.
阴性检查点调节因子 (NCR) 会调节 T 细胞对自身抗原的免疫反应，并限制自身免疫的发展。与在活化的 T 淋巴细胞上表达的所有其他 NCR 不同，含有 V 型免疫球蛋白结构域的 T 细胞激活抑制因子 (VISTA) 在幼稚 T 细胞上表达。 VISTA 参与通过促进抗原诱导的外周 T 细胞缺失来增加 T 细胞耐受性虽然 VISTA 在幼稚 T 细胞稳态中发挥着关键作用，但在炎症条件下，VISTA 抑制幼稚 T 细胞反应的能力会丧失。因此，VISTA 是初始 T 细胞的独特 NCR，对于静态维持和外周耐受性的稳态维持至关重要
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