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首页> 外文期刊>Clinical and diagnostic laboratory immunology >Endothelial Cells Expressing an Inflammatory Phenotype Are Lysed by Superantigen-Targeted Cytotoxic T Cells
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Endothelial Cells Expressing an Inflammatory Phenotype Are Lysed by Superantigen-Targeted Cytotoxic T Cells

机译：超抗原靶向的细胞毒性T细胞裂解表达炎症表型的内皮细胞。

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The objective of this study was to investigate whether the superantigen staphylococcal enterotoxin A (SEA), which binds to HLA class II and T-cell receptor Vβ chains, can direct cytotoxic T cells to lyse cytokine-stimulated endothelial cells (EC). In addition, we wanted to determine whether SEA-primed cytotoxic T cells could be targeted to EC surface molecules as a means of a novel cancer immunotherapy. Human umbilical vein EC (HUVEC), dermal microvascular EC (HMVEC), or the EC line EA.hy926 stimulated with gamma interferon (IFN-γ) or tumor necrosis factor alpha (TNF-α) displayed upregulated HLA class II and adhesion molecule (CD54 and CD106) expression, respectively. SEA-primed T cells induced a strong cytotoxicity against IFN-γ- and TNF-α-activated EA.hy926 which had been preincubated with SEA. Blocking of CD54 completely abrogated the T-cell attack. SEA-D227A, which has a mutated class II binding site, did not promote any cytotoxicity. A strong lysis was observed when a fusion protein consisting of protein A and SEA-D227A was added together with T cells to TNF-α-induced EA.hy926 and HUVEC precoated with monoclonal antibodies (MAb) directed against HLA class I, CD54, or CD106 molecules. Finally, an scFv antibody fragment reactive with an unknown EC antigen was fused with SEA-D227A. Both EA.hy926 and HMVEC were efficiently lysed by scFv-SEA-D227A-triggered cytotoxic T cells. Taken together, superantigen-activated T-cell-dependent EC killing was induced when EC expressed an inflammatory phenotype. Moreover, specific MAb targeting of the superantigen to surface antigens induced EC lysis. Our data suggest that directed T-cell-mediated lysis of unwanted proliferating EC, such as those in the tumor microvasculature, can be clinically useful.
机译：这项研究的目的是研究结合HLA II类和T细胞受体Vβ链的超抗原葡萄球菌肠毒素A（SEA）是否可以指导细胞毒性T细胞裂解细胞因子刺激的内皮细胞（EC）。此外，我们想确定SEA引发的细胞毒性T细胞是否可以靶向EC表面分子，作为新型癌症免疫疗法的一种手段。 γ-干扰素（IFN-γ）或肿瘤坏死因子α（TNF-α）刺激的人脐静脉EC（HUVEC），皮肤微血管EC（HMVEC）或EC线EA.hy926显示出上调的HLA II类和粘附分子（ CD54和CD106）表达。 SEA引发的T细胞对已与SEA预孵育的IFN-γ和TNF-α激活的EA.hy926产生强烈的细胞毒性。 CD54的阻滞完全消除了T细胞的攻击。具有突变的II类结合位点的SEA-D227A没有促进任何细胞毒性。当将由蛋白A和SEA-D227A组成的融合蛋白与T细胞一起添加到TNF-α诱导的EA.hy926和HUVEC上时，强烈裂解，预涂了针对HLA I类，CD54或HLA的单克隆抗体（MAb） CD106分子。最后，将与未知EC抗原反应的scFv抗体片段与SEA-D227A融合。 EA.hy926和HMVEC均被scFv-SEA-D227A触发的细胞毒性T细胞有效裂解。综上所述，当EC表达炎症表型时，会诱导超抗原激活的T细胞依赖性EC杀伤。而且，超抗原对表面抗原的特异性MAb靶向诱导EC裂解。我们的数据表明，定向T细胞介导的不需要的增殖性EC（例如肿瘤微脉管系统中的那些）的裂解可能在临床上有用。

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