Expression and regulation of the PD-L1 immunoinhibitory molecule on microvascular endothelial cells
Expression and regulation of the PD-L1 immunoinhibitory molecule on microvascular endothelial cells
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DOI：
10.1038/sj/mn/7800123
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发表时间：
2002-04-01
期刊：
影响因子：
2.4
通讯作者：
Leonard, JP
中科院分区：
文献类型：
--
作者：
Eppihimer, MJ;Gunn, J;Leonard, JP
目的：研究一种新的B7样蛋白PD-L1的表达和调控。免疫抑制受体PD-1的配体在活化的T细胞上表达。方法：分别用干扰素和IL-12处理体外和体内微血管内皮细胞，用双标记抗体技术检测细胞表面PD-L1的表达。结果：在基础培养条件下，内皮细胞上存在PD-L1。用干扰素-α、-β和-γ处理内皮细胞，而不用脂多糖处理内皮细胞，可诱导内皮细胞表面PD-L1的表达和mRNA水平升高。应用双标记单抗技术，检测了野生型和干扰素-γ缺陷小鼠不同组织中PD-L1的表达。IL-12攻击后24小时，PD-L1在组织中的表达显著增加，峰值出现在72小时后。IL-12不能有效地诱导干扰素-γ缺陷小鼠组织中PD-L1的表达。结论：在干扰素-α-β和-γ介导的小鼠内皮细胞上表达了一种新的B7样分子，提示内皮细胞可能通过调节T细胞功能而发挥作用。
Objective: To evaluate the expression and regulation of a novel B7-like protein, PD-L1. the ligand for the immunoinhibitory receptor PD-1 expressed on activated T-cells. on microvascular endothelial cells (ECs)Methods: PD-L1 expression on ECs in vitro and in vivo was quantified by using a dual radiolabeled antibody technique after treatment with interferons (IFN) and IL-12, respectively. Changes in the level of PD-L1 mRNA were determined by using RT-PCR.Results: PD-L1 was observed to be present on ECs under basal conditions. Treatment of ECs with IFN-alpha, -beta and -gamma but not LPS,was observed to induce elevations in the mRNA and surface expression of PD-L1 on ECs. By using a dual radiolabeled monoclonal antibody (mAb) technique., PD-L1 expression in various tissues of control and IL-12 challenged wild-type and IFN-gamma-deficient mice was measured. A significant increase in PD-L1 expression was observed in tissues at 24 hours after IL-12-challenge, with peak levels of PD-L1 occurring 72 hours aft or IL-12 challenge. IL-12 was not effective at inducing PD-L1 expression in tissues of IFN-gamma-deficient mice.Conclusions: These data show the expression of a novel B7-like molecule on murine ECs that is mediated by IFN-alpha -beta, and -gamma, and suggest a potential pathway by which ECs may modulate T-cell function.