METHODS: Isolation of cells from blood and mucosal biopsies, magnetic separation of В cells, CD4+ and CD4+CCR6+CD45RO+ T cells, antigen-specific activation, B cell response in vitro, flow cytometry, determination of CD4+CD25hiFoxP3+ Tregs and various groups of Th cells.
RESULTS: CD4+CCR6+ blood lymphocytes from healthy donors included Th cells and Tregs. These CCR6+ Th cells produced proinflammatory cytokines and also stimulated plasma cell maturation and antibody production in vitro. H. pylori gastritis and peptic ulcer disease were associated with an increase in the number of circulate CD4+CCR6+CD45RO+ cells and the percentage of Th1, Th17 and Th1/17 cells in this lymphocyte subgroup. In H. pylori-positive patients, circulating CD4+CCR6+ cells contained a higher proportion of H. pylori-specific cells compared with their CD4+CCR6- counterparts. H. pylori infection strongly increased the content of CD4+ lymphocytes in the inflamed gastric mucosa, with the majority of these CD4+ lymphocytes expressing CCR6. CD4+CCR6+ lymphocytes from H. pylori-infected stomach included Tregs and in vivo activated T cells, some of which produced interferon-γ without ex vivo stimulation.
CONCLUSIONS: H. pylori infection causes an increase in the number of mature CD4+CCR6+ lymphocytes in the blood, with a pro-inflammatory shift in their composition and enrichment of the gastric mucosa with CD4+CCR6+ lymphocytes, including CCR6+ Th1 cells and Tregs.
方法:从血液和粘膜活检中分离细胞,B细胞的磁性分离,CD4+和CD4+CCR6+CD45RO+T细胞,抗原特异性激活,体外B细胞反应,流式细胞术,测定CD4+CD25hiFoxP3+Tregs和各组Th细胞。
结果:来自健康供体的CD4+CCR6+血液淋巴细胞包括Th细胞和Tregs。这些CCR6+Th细胞产生促炎细胞因子,并且还在体外刺激浆细胞成熟和抗体产生。幽门螺杆菌胃炎和消化性溃疡疾病与该淋巴细胞亚群中循环CD4CCR6CD45RO细胞数量和Th1,Th17和Th1/17细胞百分比的增加有关。在幽门螺杆菌阳性患者中,循环CD4+CCR6+细胞中幽门螺杆菌特异性细胞的比例高于CD4+CCR6-细胞.幽门螺杆菌感染强烈增加了发炎的胃粘膜中CD4+淋巴细胞的含量,这些CD4+淋巴细胞中的大多数表达CCR6。来自幽门螺杆菌感染胃的CD4+CCR6+淋巴细胞包括Tregs和体内活化的T细胞,其中一些在没有离体刺激的情况下产生干扰素-γ。
结论:H.幽门螺杆菌感染导致血液中成熟CD4+CCR6+淋巴细胞数量增加,随着其组成的促炎变化和CD4+CCR6+淋巴细胞的胃粘膜富集,包括CCR6+Th1细胞和Tregs。