ICOS-ligand, expressed on human endothelial cells, costimulates Th1 and Th2 cytokine secretion by memory CD4+ T cells
ICOS-ligand, expressed on human endothelial cells, costimulates Th1 and Th2 cytokine secretion by memory CD4+ T cells
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DOI：
10.1073/pnas.092576699
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发表时间：
2002-04-30
影响因子：
11.1
通讯作者：
Mages, HW
中科院分区：
文献类型：
--
作者：
Khayyamian, S;Hutloff, A;Mages, HW
尽管缺乏经典的共刺激配体CD80和CD86，但内皮细胞(EC)在炎性免疫反应中发挥着核心作用，并有效地诱导T细胞的效应功能。利用hIL-131单抗，我们证明了人可诱导共刺激分子-配体(ICOS-L)是一种与CD80/CD86相关的分子，在活体内人内皮细胞上有结构性表达。在体外，炎性细胞因子肿瘤坏死因子α和IL-1β对人脐静脉内皮细胞和微血管内皮细胞ICOS-L的表达有强烈的促进作用，而CD_(40)和脂多糖刺激内皮细胞的作用较弱。在超抗原存在下，MHC II+EC与静止记忆CD4(+)T细胞共培养后，T细胞表面ICOS表达明显上调，并产生Th1(干扰素-γ、IL-2)和Th2细胞因子(IL-4、IL-10、IL-13)。当与抑制性单抗hIL-131共培养时，所有细胞因子的分泌减少约50-80%，表明ICOS-L是EC介导的T细胞活化的主要共刺激分子。综上所述，我们的数据提示ICOS-L在重新激活内皮上的效应/记忆T细胞以控制免疫细胞进入炎症组织中起着重要的生理作用。
Endothelial cells (EC) play a central role in inflammatory immune responses and efficiently induce effector functions in T cells, despite lacking the classical costimulatory ligands CD80 and CD86. By using the mAb HIL-131 we now demonstrate that human inducible costimulator-ligand (ICOS-L), a molecule related to CD80/CD86, is constitutively expressed on human EC in vivo. In vitro, ICOS-L expression was strongly enhanced on human umbilical vein EC and microvascular EC by the inflammatory cytokines tumor necrosis factor alpha and IL-1beta, and to a lower extent by stimulation of EC by CD40 or lipopolysaccharide. Coculture of MHC class II+ EC with resting memory CD4(+) T cells in the presence of superantigen led to a marked up-regulation of ICOS on T cells and to the production of Th1 (IFN-gamma, IL-2) and Th2 cytokines (IL-4, IL-10, IL-13). When these cocultures were performed in the presence of the inhibitory mAb HIL-131, secretion of all cytokines was reduced by about 50-80%, indicating that ICOS-L is a major costimulator in EC-mediated T cell activation. Taken together, our data suggest an important physiological role of ICOS-L in the reactivation of effector/memory T cells on the endothelium controlling the entry of immune cells into inflamed tissue.