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Helicobacter pylori-Specific CD4+ T Cells Home to and Accumulate in the Human Helicobacter pylori-Infected Gastric Mucosa

机译:幽门螺杆菌特异的CD4 + T细胞在人类幽门螺杆菌感染的胃粘膜中形成并积累

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Helicobacter pylori infects the stomach and duodenal mucosa. T cells are important components of the H. pylori-induced immune response, but little is currently known about how these cells are recruited to the infected mucosa. Here, we have characterized stomach and duodenal T cells isolated from H. pylori-infected and noninfected subjects with regard to subtype, expression of homing and chemokine receptors, and in vitro reactivity to H. pylori antigens. Higher numbers of CD4+ but similar numbers of CD8+ lamina propria T cells were isolated from stomach biopsies from H. pylori-positive compared to H. pylori-negative individuals. CD4+ T cells from infected stomach expressed increased levels of the homing receptor L-selectin and the chemokine receptor CCR4 compared to CD4+ T cells from uninfected stomach. Infected stomach mucosa also contained increased levels of the CCR4 chemokine ligand MDC/CCL22. In contrast, comparable numbers of CD4+ T cells with similar receptor expression were isolated from the duodenum of H. pylori-positive and H. pylori-negative individuals. In vitro proliferation of mucosal T cells was strongly enhanced by the addition of interleukin-2 (IL-2) and IL-7 to the cell cultures. Using this approach, H. pylori-specific T-cell responses were detected in stomach CD4+ T cells from H. pylori-positive but not H. pylori-negative individuals. Duodenal T cells from only a few individuals responded to H. pylori stimulation, and the responsiveness was not restricted to H. pylori-positive individuals, suggesting limited H. pylori specificity in the duodenum and possible cross-reactivity with antigens from other bacteria in this compartment. In conclusion, these results suggest that H. pylori-specific CD4+ T cells preferentially home to and accumulate in the infected stomach and that L-selectin and CCR4/MDC are important for this recruitment.
机译:幽门螺杆菌感染胃和十二指肠粘膜。 T细胞是 H的重要组成部分。幽门螺杆菌诱导的免疫反应,但目前关于这些细胞如何募集到感染的粘膜的了解甚少。在这里,我们表征了从 H分离的胃和十二指肠T细胞。幽门螺杆菌感染和未感染受试者的亚型,归巢和趋化因子受体的表达以及对 H的体外反应性。幽门螺杆菌抗原。从 H的胃活检中分离出更多数量的CD4 + ,但数量相似的CD8 + 固有层T细胞。幽门螺杆菌阳性( H)。幽门螺杆菌阴性个体。与未感染胃的CD4 + T细胞相比,感染胃的CD4 + T细胞表达的归巢受体L-选择蛋白和趋化因子受体CCR4水平升高。感染的胃粘膜也含有增加水平的CCR4趋化因子配体MDC / CCL22。相反,从 H的十二指肠中分离出可比较数量的具有相似受体表达的CD4 + T细胞。幽门螺杆菌阳性和 H。幽门螺杆菌阴性个体。通过向细胞培养物中添加白介素-2(IL-2)和IL-7,粘膜T细胞的体外增殖得到了极大的增强。使用这种方法, H。在 H的胃CD4 + T细胞中检测到幽门螺旋菌特异性的T细胞应答。幽门螺旋菌阳性但不是 H。幽门螺杆菌阴性个体。只有少数个体的十二指肠T细胞对 H有反应。幽门螺杆菌刺激,并且反应性不仅限于 H。幽门螺杆菌阳性的个体,提示 H有限。十二指肠中的幽门螺杆菌特异性,并可能与该隔室中其他细菌的抗原发生交叉反应。总之,这些结果表明 H。幽门螺杆菌特异的CD4 + T细胞优先归巢并在受感染的胃中积累,因此L-选择蛋白和CCR4 / MDC对于这种募集至关重要。

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