Helicobacter pylori gastritis in children is associated with a regulatory T-cell response

Gastroenterology. 2008 Feb;134(2):491-9. doi: 10.1053/j.gastro.2007.11.006. Epub 2007 Nov 4.

Abstract

Background & aims: Helicobacter pylori infection in children infrequently causes gastroduodenal mucosal ulceration. Because H pylori induces T-cell dependent gastric inflammation in adults and T regulatory (Treg) cells suppress T-cell-dependent pathology, we evaluated gastric histopathology and Treg cell responses in H pylori-infected children and adults.

Methods: Gastric tissue from 36 children and 79 adults with abdominal symptoms in Santiago, Chile, was evaluated prospectively for H pylori bacteria and histopathology using the Sydney classification and Treg responses using immunoassay, immunohistochemistry, and real-time polymerase chain reaction.

Results: Eighteen (50%) of the children and 51 (65%) of the adults were infected with H pylori. Children and adults were colonized with similar levels of H pylori. However, the level of gastritis in the children was reduced substantially compared with that of the adults (P < .05). Coincident with reduced gastric inflammation, the number of Treg cells and levels of Treg cytokines (transforming growth factor [TGF]-beta1 and interleukin-10) were increased markedly in the gastric mucosa of H pylori-infected children compared with that of infected adults (P < .03 and < .05, respectively). Also, H pylori infection in the children was associated with markedly increased levels of gastric TGF-beta1 and interleukin-10 messenger RNA. Importantly, gastric TGF-beta1 in H pylori-infected children localized predominantly to mucosal CD25(+) and Foxp3(+) cells, indicating a Treg source for the TGF-beta1.

Conclusions: Gastric pathology is reduced and local Treg cell responses are increased in H pylori-infected children compared with infected adults, suggesting that gastric Treg cell responses down-regulate the inflammation and ulceration induced by H pylori in children.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aging / pathology
  • Cell Proliferation
  • Child
  • Chile
  • Down-Regulation
  • Female
  • Forkhead Transcription Factors / metabolism
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology
  • Gastric Mucosa / virology
  • Gastritis / etiology
  • Gastritis / immunology*
  • Gastritis / virology*
  • Helicobacter Infections / complications
  • Helicobacter Infections / immunology*
  • Helicobacter Infections / pathology
  • Helicobacter pylori / pathogenicity*
  • Humans
  • Interleukin-10 / metabolism
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Male
  • Prospective Studies
  • RNA, Messenger / metabolism
  • T-Lymphocytes, Regulatory / pathology*
  • T-Lymphocytes, Regulatory / physiology*
  • T-Lymphocytes, Regulatory / virology
  • Transforming Growth Factor beta1 / metabolism

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-2 Receptor alpha Subunit
  • RNA, Messenger
  • Transforming Growth Factor beta1
  • Interleukin-10