CD25+/Foxp3+ T cells regulate gastric inflammation and Helicobacter pylori colonization in vivo
CD25+/Foxp3+ T cells regulate gastric inflammation and Helicobacter pylori colonization in vivo
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DOI：
10.1053/j.gastro.2006.05.001
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发表时间：
2006-08-01
期刊：
影响因子：
29.4
通讯作者：
Prinz, Christian
中科院分区：
文献类型：
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作者：
Rad, Roland;Brenner, Lena;Prinz, Christian
背景与目标：幽门螺杆菌感染世界上一半以上的人口。与大多数其他病原体不同，这种微生物在其宿主的虚拟生命周期中持续存在。目前尚不清楚为什么免疫系统无法消除感染，但最近的研究表明CD4(+)/CD25(+)/Foxp3(+)调节性T细胞可能参与了这一过程。方法：通过使用感染小鼠模型和 108 名患者的胃活检，我们对螺杆菌诱导的 CD25(+)/Foxp3(+) T 细胞反应进行了详细的描述性和功能表征。结果：在 C57BL/6 小鼠中，幽门螺杆菌诱导了显着的胃 Foxp3(+) T 细胞反应，这种反应在几个月内随着炎症的严重程度而增加，直到建立稳定的稳态情况。因此，在幽门螺杆菌感染的患者中，但在未感染的个体中，免疫组织化学检测到了大量的胃Foxp3(+) T细胞。为了确定这种反应的功能性体内相关性，使用抗CD25单克隆抗体(PC61)在小鼠体内系统性地去除CD25(+)细胞。感染后 4 周，PC61 治疗的小鼠（而非未治疗的动物）出现了严重的胃炎，且细胞因子表达升高，粘膜 T 细胞、B 细胞和巨噬细胞数量增加。与此同时，PC61 治疗小鼠血清中幽门螺杆菌特异性 IgG1 和 IgG2c 抗体的滴度增加。 CD25 耗尽的小鼠胃部炎症反应的增加与细菌负荷的减少有关。结论：CD25(+)/Foxp3(+) T细胞积极参与针对H pylori的免疫应答。受感染小鼠体内这些细胞的消耗会导致胃部炎症增加并减少细菌定植。
Background & Aims: Helicobacter pylori infects more than half of the world's population. In contrast to most other pathogens, the microbe persists for the virtual life of its host. It is unclear why the immune system is unable to eliminate the infection, but recent studies suggested that CD4(+)/CD25(+)/Foxp3(+) regulatory T cells may be involved in this process. Methods: By using a mouse model of infection and gastric biopsies from 108 patients, we performed a detailed descriptive and functional characterization of the Helicobacter-induced CD25(+)/Foxp3(+) T-cell response. Results: In C57BL/6 mice, H pylori induced a marked gastric Foxp3(+) T-cell response, which increased over several months together with the severity of inflammation, until a stable homeostatic situation became established. Accordingly, in Helicobacter-infected patients, but not in uninfected individuals, large numbers of gastric Foxp3(+) T cells were detected immunohistochemically. To define the functional in vivo relevance of this response, CD25(+) cells were depleted systemically in mice by using an antiCD25 monoclonal antibody (PC61). Already 4 weeks after infection, PC61-treated mice, but not untreated animals, developed a severe gastritis with heightened cytokine expression and increased numbers of mucosal T cells, B cells, and macrophages. This was accompanied by increased titers of H pylori-specific IgG1 and IgG2c antibodies in the sera of PC61-treated mice. This increased gastric inflammatory response in CD25-depleted mice was associated with reduced bacterial loads. Conclusions: CD25(+)/Foxp3(+) T cells actively participate in the immune response to H pylori. In vivo depletion of these cells in infected mice leads to increased gastric inflammation and reduced bacterial colonization.