B7-H1 is expressed by human endothelial cells and suppresses T cell cytokine synthesis
B7-H1 is expressed by human endothelial cells and suppresses T cell cytokine synthesis
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DOI：
10.4049/jimmunol.169.7.3581
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发表时间：
2002-10-01
影响因子：
4.4
通讯作者：
Hughes, CCW
中科院分区：
文献类型：
--
作者：
Mazanet, MM;Hughes, CCW
人内皮细胞(ECs)提供的共刺激信号足以激活静止的记忆T细胞产生IL-2和干扰素-γ，至少部分通过CD58-CD2相互作用。最近，B7样分子B7-H1(PD-L1)被描述并被证明调节T细胞的激活；然而，关于它的报道却相互矛盾。它是刺激还是抑制T细胞细胞因子的合成。B7-H1不受内皮细胞的组成性表达，但在干扰素-γ的诱导下迅速表达，并在干扰素-γ和肿瘤坏死因子的协同作用下表达。在发炎的皮肤中，B7-H1由微血管亚群和角质形成细胞表达，但在正常皮肤中几乎检测不到。阻断EC表达的B7-H1与其T细胞配体程序性死亡-1(PD-1)的相互作用，使用PD-1-Fc融合蛋白，或通过吗啉反义寡核苷酸阻断B7-H1的表达，增加IL-2和干扰素-γ的表达，暗示B7-H1是细胞因子合成的负调控因子。然而，通过PD-1的信号并不影响T细胞上CD25或CD69激活标记的诱导，这表明它的作用是细胞因子合成的特异性。B7-H1对细胞因子表达的抑制作用与原始刺激的强度成正比，允许B7-H1决定T细胞对ECs的激活水平。我们的结果表明，B7-H1对ECs激活的T细胞的细胞因子合成具有负性调节作用。
Human endothelial cells (ECs) provide costimulatory signals sufficient to activate resting memory T cells to produce IL-2 and IFN-gamma, at least in part through CD58-CD2 interactions. Recently, the B7-like molecule, B7-H1 (PD-L1), was described and shown to regulate T cell activation; however, there are conflicting reports on. whether it stimulates or inhibits T cell cytokine synthesis. B7-H1 is not expressed constitutively by ECs; however, it is rapidly induced by IFN-gamma, and synergistically by IFN-gamma and TNF. In inflamed skin, B7-H1 is expressed by a subset of microvessels, and by keratinocytes, but is barely detectable in normal skin. Blocking the interaction of EC-expressed B7-H1 with its T cell ligand, programmed death-1 (PD-1), using a PD-1-Fc fusion protein, or by blocking B7-H1 expression with morpholino antisense oligonucleotides, augments expression of IL-2 and IFN-gamma, implicating B7-H1 as a negative regulator of cytokine synthesis. However, signaling through PD-1 does not affect induction of the activation markers CD25 or CD69 on T cells, suggesting that its effects are specific to cytokine synthesis. The suppressive effects of B7-H1 on cytokine expression are proportional to the strength of the primary stimulus, allowing for B7-H1 to determine the level of T cell activation in response to ECs. Our results demonstrate that B7-H1 negatively regulates cytokine synthesis in T cells activated by ECs.