Naturally occurring regulatory T cells (CD4+, CD25high, FOXP3+) in the antrum and cardia are associated with higher H-pylori colonization and increased gene expression of TGF-β1
Naturally occurring regulatory T cells (CD4+, CD25high, FOXP3+) in the antrum and cardia are associated with higher H-pylori colonization and increased gene expression of TGF-β1
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DOI：
10.1111/j.1523-5378.2008.00612.x
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发表时间：
2008-08-01
期刊：
影响因子：
4.4
通讯作者：
Malfertheiner, Peter
中科院分区：
文献类型：
--
作者：
Kandulski, Arne;Wex, Thomas;Malfertheiner, Peter
背景：幽门螺杆菌引起胃部炎症。尽管诱导了幽门螺杆菌特异性B细胞和T细胞，但免疫反应不足以清除感染。调节性T细胞（Treg细胞）抑制抗原特异性T细胞的激活和增殖，介导免疫耐受。FOXP3被证明在Treg细胞的一个亚群中表达，称为“自然发生的Treg细胞”。这些细胞在幽门螺杆菌引起的人胃粘膜炎症中还没有得到充分的研究。材料和方法：本研究纳入76例患者，根据有无幽门螺旋杆菌进行分层。采用实时定量聚合酶链反应分析胃窦、胃体和贲门活检组织中FOXP3、转化生长因子(TGF)- β 1和白细胞介素-10的基因表达水平。免疫组化分析FOXP3的表达。综合统计分析表达水平的差异，并与临床和组织形态学参数相关。结果：幽门螺杆菌阳性患者显示FOXP3转录水平在胃窦和贲门诱导19- 25倍（p < 0.02）。FOXP3转录物水平与炎症（p < .04）和tgf - β 1转录物水平呈正相关（p < .001）。此外，FOXP3(+) Treg细胞与幽门螺杆菌定植呈正相关。结论：本研究表明幽门螺杆菌诱导的胃炎与FOXP3(+) Treg细胞的募集有关，FOXP3(+) Treg细胞的募集与细菌定植程度和粘膜tgf - β 1表达有关。总之，这些数据支持了FOXP3(+) Treg细胞在人类幽门螺杆菌感染的终身持续中发挥作用的假设。
Background: Helicobacter pylori causes gastric inflammation. Despite the induction of H. pylori-specific B- and T cells, the immune response is not sufficient to clear the infection. Regulatory T cells (Treg cells) suppress the activation and proliferation of antigen-specific T cells and mediate immunologic tolerance. FOXP3 was shown to be expressed in a subset of Treg cells known as 'naturally occurring Treg cells'. These cells have not been sufficiently studied in context to H. pylori-induced inflammation in human gastric mucosa.Materials and methods: The study included 76 patients stratified according to the presence of H. pylori. Gene expression levels of FOXP3, transforming growth factor (TGF)-beta 1, and interleukin-10 were analyzed by quantitative real-time polymerase chain reaction in biopsies from gastric antrum, corpus, and cardia. FOXP3 expression was also analyzed by immunohistochemistry. Differences in expression levels were analyzed by comprehensive statistical analyses and correlated with clinical and histomorphologic parameters.Results: H. pylori-positive patients revealed a 19- to 25-fold induction of FOXP3 transcript levels in antrum and cardia (p < .02). FOXP3 transcript levels correlated positively with inflammation (p < .04) and TGF-beta 1 transcript levels (p < .001). Furthermore, a positive correlation between FOXP3(+) Treg cells and H. pylori colonization was demonstrated.Conclusion: This study demonstrates that H. pylori-induced gastritis is associated with a recruitment of naturally occurring FOXP3(+) Treg cells that correlates with the degree of bacterial colonization and mucosal TGF-beta 1 expression. Together, these data support the hypothesis that naturally FOXP3(+) Treg cells play a role in the lifelong persistence of H. pylori infection in humans.