Expression of the programmed death ligand 1, b7-h1,on gastric epithelial cells after Helicobacter pylori exposure promotes development of CD4+ CD25+ FoxP3+ regulatory T cells

Expression of the programmed death ligand 1, b7-h1,on gastric epithelial cells after Helicobacter pylori exposure promotes development of CD4+ CD25+ FoxP3+ regulatory T cells
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DOI:
10.1128/iai.00553-07
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发表时间:
2007-09-01
影响因子:
3.1
通讯作者:
Reyes, Victor E.
Reyes, Victor E.
中科院分区:
医学2区
文献类型:
--
作者:
Beswick, Ellen J.;Pinchuk, Irina V.;Reyes, Victor E.

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在幽门螺杆菌感染期间,T细胞被募集到胃粘膜,但宿主T细胞应答不足以清除感染。一些募集的T细胞以极化的方式响应Th 1应答,而另一些则变得无反应性。我们先前已经表明,T细胞无反应性可能是在感染过程中通过T细胞与B7-H1的相互作用而诱导的,B7-H1在H.幽门感染最近,在H.幽门螺杆菌感染患者虽然Treg细胞在维持耐受性方面很重要,但它们也可以抑制感染期间的免疫反应。在这项研究中,我们检测了当初始T细胞与暴露于U的胃上皮细胞孵育时Treg表型的诱导。幽门。当用单克隆抗体阻断B7-H1或用小干扰RNA阻断其表达时,这种表型的频率显著降低。当这些细胞与活化的T细胞共培养时,在增殖测定中评估这些Treg细胞的功能作用,这有效地降低了细胞的增殖。
During Helicobacter pylori infection, T cells are recruited to the gastric mucosa, but the host T-cell response is not sufficient to clear the infection. Some of the recruited T cells respond in a polarized manner to a Th1 response, while others become anergic. We have previously shown that T-cell anergy may be induced during infection by the interaction of T cells with B7-H1, which is up-regulated on the gastric epithelium during H. pylori infection. Recently, regulatory T (Treg) cells with a CD4(+) CD25(high) FoxP3(+) phenotype were found at an increased frequency in the gastric mucosa of biopsy specimens from H. pylori-infected patients. While Treg cells are important in maintaining tolerance, they can also suppress immune responses during infection. In this study, we examined the induction of the Treg phenotype when naive T cells were incubated with gastric epithelial cells exposed to U. pylori. The frequency of this phenotype was markedly decreased when B7-H1 was blocked with monoclonal antibodies or its expression was blocked with small interfering RNA. The functional role of these Treg cells was assessed in proliferation assays when the cells were cocultured with activated T cells, which effectively decreased proliferation of the cells.