首页> 美国卫生研究院文献>The Journal of Clinical Investigation >Expression of B7-1 and B7-2 costimulatory molecules by human gastric epithelial cells: potential role in CD4+ T cell activation during Helicobacter pylori infection.
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Expression of B7-1 and B7-2 costimulatory molecules by human gastric epithelial cells: potential role in CD4+ T cell activation during Helicobacter pylori infection.

机译:B7-1和B7-2共刺激分子在人胃上皮细胞中的表达:幽门螺杆菌感染过程中CD4 + T细胞活化的潜在作用。

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摘要

Human gastric mucosal epithelial cells display class II MHC, the expression of which is increased during Helicobacter pylori infection. These observations suggest that the gastric epithelium may participate as antigen-presenting cells (APC) during local immune responses. The increase in class II MHC expression occurs in parallel with an elevation in gastric CD4+ T cell numbers within and adjacent to the epithelium. Since the expression of either B7-1 (CD80) or B7-2 (CD86) on APC is required for the activation of T cells, it was important to establish human gastric epithelial cells expressed those surface ligands. The expression of B7-1 and B7-2 was detected on human gastric epithelial cell lines and freshly isolated epithelial cells from gastric biopsies with specific antibodies. B7-2 expression was higher than B7-1 at both protein and transcript levels and was increased after crosslinking class II MHC molecules on IFNgamma-treated epithelial cells and in cells pretreated with the combination of IFNgamma and H. pylori. Similarly, B7-2 expression was higher on gastric epithelial cells from H. pylori-infected tissues compared with those from uninfected specimens. To determine the function of these molecules on gastric epithelial cells, antibodies to B7-1 and B7-2 were shown to reduce the ability of the cells to stimulate alloreactive CD4+ T cells. These observations are the first to demonstrate that B7-1 and B7-2 are expressed on mucosal epithelial cells in situ. Thus, the expression of B7-1 and B7-2 by epithelial cells may allow them to act as APC in regulating local responses such as those that occur during infection with H. pylori.
机译:人胃粘膜上皮细胞显示II类MHC,在幽门螺杆菌感染期间其表达增加。这些观察结果表明,胃上皮细胞可能在局部免疫应答过程中作为抗原呈递细胞(APC)参与。 II类MHC表达的增加与上皮细胞内部和邻近的胃CD4 + T细胞数量的增加同时发生。由于激活T细胞需要在APC上表达B7-1(CD80)或B7-2(CD86),因此建立表达这些表面配体的人胃上皮细胞非常重要。在人胃上皮细胞系和用特异性抗体从胃活检组织中新鲜分离的上皮细胞上检测到B7-1和B7-2的表达。 B7-2的表达在蛋白质和转录本水平上均高于B7-1,并且在IFNγ处理的上皮细胞上以及在IFNγ和幽门螺杆菌组合预处理的细胞中使II类MHC分子交联后增加。同样,与未感染标本相比,幽门螺杆菌感染组织的胃上皮细胞中的B7-2表达更高。为了确定这些分子在胃上皮细胞上的功能,已显示针对B7-1和B7-2的抗体可降低细胞刺激同种反应性CD4 + T细胞的能力。这些观察结果首次证明B7-1和B7-2在黏膜上皮细胞中原位表达。因此,上皮细胞表达B7-1和B7-2可能使它们充当APC来调节局部反应,例如在幽门螺杆菌感染期间发生的反应。

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