Naturally occurring regulatory T cells (CD4(+), CD25(high), FOXP3(+)) in the antrum and cardia are associated with higher H-pylori colonization and increased gene expression of TGF-beta 1

作者：Kandulski Arne; Wex Thomas^*; Kuester Doerthe; Peitz Ulrich; Gebert Ingrid; Roessner Albert; Malfertheiner Peter

来源：Helicobacter, 2008, 13(4): 295-303.

DOI：10.1111/j.1523-5378.2008.00612.x

• Helicobacter pylori
• regulatory T cells
• FOXP3
• TGF-beta 1

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.

• 出版日期2008-8