%0 Journal Article %A K Robinson %A R Kenefeck %A E L Pidgeon %A S Shakib %A S Patel %A R J Polson %A A M Zaitoun %A J C Atherton %T Helicobacter pylori-induced peptic ulcer disease is associated with inadequate regulatory T cell responses %D 2008 %R 10.1136/gut.2007.137539 %J Gut %P 1375-1385 %V 57 %N 10 %X Background and aims: Helicobacter pylori infection is the major cause of peptic ulceration and gastric adenocarcinoma. To address the hypothesis that the human acquired immune response to H pylori influences pathogenesis, we characterised the gastric T helper (Th) and regulatory T cell (Treg) response of infected patients.Methods: The human gastric CD4+ T cell response of 28 donors who were infected with H pylori and 44 who were not infected was analysed using flow cytometry. The T cell associated mucosal cytokine response was analysed by real-time polymerase chain reaction assay of samples from 38 infected and 22 uninfected donors. Recombinant interleukin 10 (IL10) was added to co-cultures of H pylori and AGS cells and its suppressive effects upon inflammatory responses were measured.Results: We found that the H pylori-specific response consists of both T helper 1 and 2 subsets with high levels of IL10-secreting Tregs. People with peptic ulcer disease had a 2.4-fold reduced CD4+CD25hiIL10+ Treg response (p = 0.05) but increased Th1 and Th2 responses (Th1: 3.2-fold, p = 0.038; Th2: 6.1-fold, p = 0.029) compared to those without ulcers. In vitro studies showed that IL10 inhibited IL8 expression and activation of nuclear factor kappa B induced by H pylori in gastric epithelial cells, and enhanced H pylori growth in a bacterial-cell co-culture model.Conclusions: Together our data suggest that H pylori induces a regulatory T cell response, possibly contributing to its peaceful coexistence with the human host, and that ulcers occur when this regulatory response is inadequate. %U https://gut.bmj.com/content/gutjnl/57/10/1375.full.pdf