VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses.
VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses.
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DOI：
10.1084/jem.20100619
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发表时间：
2011-03-14
期刊：
影响因子：
--
通讯作者：
Noelle RJ
中科院分区：
文献类型：
--
作者：
Wang L;Rubinstein R;Lines JL;Wasiuk A;Ahonen C;Guo Y;Lu LF;Gondek D;Wang Y;Fava RA;Fiser A;Almo S;Noelle RJ
VISTA抑制T细胞增殖和细胞因子产生，并可影响小鼠的自身免疫和抗肿瘤反应。免疫球蛋白（IG）超家族由许多关键的免疫调节剂组成，包括B7家族配体和受体。在这项研究中，我们确定了一种新的和结构独特的IG超家族抑制配体，其胞外结构域具有同源性的B7家族配体PD-L1。该分子被命名为T细胞活化的V结构域IG抑制因子（VISTA）。VISTA主要在造血细胞上表达，并且VISTA表达在骨髓抗原呈递细胞（APC）和T细胞上高度调节。APC上的可溶性VISTA-Ig融合蛋白或VISTA表达在体外抑制T细胞增殖和细胞因子产生。VISTA特异性单克隆抗体在体外通过表达VISTA的APC干扰VISTA诱导的T细胞应答抑制。此外，抗VISTA治疗加剧小鼠中T细胞介导的自身免疫疾病实验性自身免疫性脑脊髓炎的发展。最后，肿瘤细胞上的VISTA过表达干扰小鼠体内的保护性抗肿瘤免疫。这些发现表明，VISTA是一种新型免疫调节分子，具有与其他IG超家族成员非冗余的功能活性，并可能在癌症的自身免疫和免疫监视的发展中发挥作用。
VISTA suppresses T cell proliferation and cytokine production and can influence autoimmunity and antitumor responses in mice. The immunoglobulin (Ig) superfamily consists of many critical immune regulators, including the B7 family ligands and receptors. In this study, we identify a novel and structurally distinct Ig superfamily inhibitory ligand, whose extracellular domain bears homology to the B7 family ligand PD-L1. This molecule is designated V-domain Ig suppressor of T cell activation (VISTA). VISTA is primarily expressed on hematopoietic cells, and VISTA expression is highly regulated on myeloid antigen-presenting cells (APCs) and T cells. A soluble VISTA-Ig fusion protein or VISTA expression on APCs inhibits T cell proliferation and cytokine production in vitro. A VISTA-specific monoclonal antibody interferes with VISTA-induced suppression of T cell responses by VISTA-expressing APCs in vitro. Furthermore, anti-VISTA treatment exacerbates the development of the T cell–mediated autoimmune disease experimental autoimmune encephalomyelitis in mice. Finally, VISTA overexpression on tumor cells interferes with protective antitumor immunity in vivo in mice. These findings show that VISTA, a novel immunoregulatory molecule, has functional activities that are nonredundant with other Ig superfamily members and may play a role in the development of autoimmunity and immune surveillance in cancer.
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Searle S