Helicobacter pylori-induced peptic ulcer disease is associated with inadequate regulatory T-cell responses
Karen Robinson 1*, Rupert Kenefeck 1, Emma Pidgeon 1, Saba Shakib 1, Sapna Patel 1, Robin Polson 1, Abed M Zaitoun 1 and John C Atherton 1
1 University of Nottingham, United Kingdom
* To whom correspondence should be addressed. E-mail: karen.robinson{at}nottingham.ac.uk.
Accepted 25 April 2008
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Background & 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 H. pylori-infected and 44 uninfected donors was analysed using flow cytometry. The T-cell associated mucosal cytokine response was analysed by real-time PCR assay of samples from 38 infected and 22 uninfected donors. Recombinant IL-10 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 interleukin-10-secreting Tregs. Individuals with peptic ulcer disease had a 2.4-fold reduced CD4+CD25hiIL-10+ 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 IL-10 inhibited H. pylori-induced gastric epithelial cell IL-8 expression and NF-kB activation, 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.
