Helicobacter pylori-induced peptic ulcer disease is associated with inadequate regulatory T cell responses
- K Robinson1,2,
- R Kenefeck1,2,
- E L Pidgeon1,
- S Shakib1,
- S Patel1,2,
- R J Polson1,
- A M Zaitoun2,3,
- J C Atherton1,2
- 1Institute of Infection, Immunity & Inflammation, University of Nottingham, Centre for Biomolecular Sciences, Nottingham, UK
- 2Wolfson Digestive Diseases Centre, University of Nottingham, Queen’s Medical Centre, Nottingham, UK
- 3Department of Histopathology, University of Nottingham, Queen’s Medical Centre, Nottingham, UK
- Dr K Robinson, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, NG7 2RD, UK;
- Revised 2 April 2008
- Accepted 25 April 2008
- Published Online First 8 May 2008
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.
Funding: This work was supported by the Medical Research Council (G0601170) and an award from the University of Nottingham.
Competing interests: None.
Ethics approval: The use of the patient samples for this study was approved by the Nottingham University Hospital Ethics Committee on 16 January 2001.