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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >VSIG-3 as a ligand of VISTA inhibits human T-cell function
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VSIG-3 as a ligand of VISTA inhibits human T-cell function

机译：VSIG-3作为Vista的配体抑制人T细胞功能

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B7 family members and their receptors play a central role in the regulation of T-cell responses through T-cell co-stimulation and co-inhibition pathways that constitute attractive targets for the development of immunotherapeutic drugs. In this study, we report that VSIG-3/IGSF11 is a ligand of B7 family member VISTA/PD-1H and inhibits human T-cell functions through a novel VSIG-3/VISTA pathway. An extensive functional ELISA binding screening assay reveals that VSIG-3 binds to the new B7 family member VISTA but does not interact with other known members of the B7 family. Under the same experimental conditions, we did not observe any significant interaction between VSIG-8 and VISTA. In addition, VSIG-3 inhibits human T-cell proliferation in the presence of T-cell receptor signaling. Furthermore, VSIG-3 significantly reduces cytokine and chemokine production by human T cells including IFN-, IL-2, IL-17, CCL5/Rantes, CCL3/MIP-1, and CXCL11/I-TAC. Anti-VISTA neutralization antibodies attenuate the binding of VSIG-3 and VISTA, as well as VSIG-3-induced T-cell inhibition. Hence, we have identified a novel ligand for VISTA that is able to inhibit human T-cell proliferation and cytokine production. This unique VSIG-3/VISTA co-inhibitory pathway may provide new strategies for the treatment of human cancers, autoimmune disorders, infection, and transplant rejection and may aid in the design of better vaccines.
机译：B7家族成员及其受体在通过T细胞共刺激和共同抑制途径调节T细胞反应中发挥着核心作用，该途径构成了可吸引人的免疫治疗药物的诱导目标。在该研究中，我们报告了Vsig-3 / IgSF11是B7家族成员Vista / Pd-1H的配体，并通过新的Vsig-3 / Vista途径抑制人T细胞功能。广泛的功能性ELISA结合筛选测定显示，Vsig-3与新的B7家族成员Vista结合，但不会与B7家族的其他已知成员相互作用。在相同的实验条件下，我们没有观察到VSIG-8和Vista之间的任何显着互动。此外，Vsig-3在存在T细胞受体信号传导的情况下抑制人T细胞增殖。此外，Vsig-3通过IFN-，IL-2，IL-17，CCL5 / RANTES，CCL3 / MIP-1和CXCL11 / I-TAc显着降低了人体T细胞的细胞因子和趋化因子产生。抗Vista中和抗体衰减Vsig-3和Vista的结合，以及Vsig-3诱导的T细胞抑制作用。因此，我们已经确定了一种能够抑制人T细胞增殖和细胞因子产生的Vista的新型配体。这种独特的Vsig-3 / Vista共同抑制途径可以为治疗人类癌症，自身免疫障碍，感染和移植排斥提供新的策略，并且可以帮助设计更好的疫苗。

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