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Helicobacter pylori-induced peptic ulcer disease is associated with inadequate regulatory T cell responses
  1. K Robinson1,2,
  2. R Kenefeck1,2,
  3. E L Pidgeon1,
  4. S Shakib1,
  5. S Patel1,2,
  6. R J Polson1,
  7. A M Zaitoun2,3,
  8. J C Atherton1,2
  1. 1
    Institute of Infection, Immunity & Inflammation, University of Nottingham, Centre for Biomolecular Sciences, Nottingham, UK
  2. 2
    Wolfson Digestive Diseases Centre, University of Nottingham, Queen’s Medical Centre, Nottingham, UK
  3. 3
    Department of Histopathology, University of Nottingham, Queen’s Medical Centre, Nottingham, UK
  1. Dr K Robinson, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, NG7 2RD, UK; karen.robinson{at}nottingham.ac.uk

Abstract

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.

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Footnotes

  • 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.

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