Complex T cell interactions contribute to Helicobacter pylori gastritis in mice

Infect Immun. 2013 Mar;81(3):740-52. doi: 10.1128/IAI.01269-12. Epub 2012 Dec 21.

Abstract

Disease due to the gastric pathogen Helicobacter pylori varies in severity from asymptomatic to peptic ulcer disease and cancer. Accumulating evidence suggests that one source of this variation is an abnormal host response. The goal of this study was to use a mouse model of H. pylori gastritis to investigate the roles of regulatory T cells (Treg) as well as proinflammatory T cells (Th1 and Th17) in gastritis, gastric T cell engraftment, and gastric cytokine production. Our results support published data indicating that severe gastritis in T cell recipient mice is due to failure of Treg engraftment, that Treg ameliorate gastritis, and that the proinflammatory response is attributable to interactions between several cell subsets and cytokines. We confirmed that gamma interferon (IFN-γ) is essential for induction of gastritis but showed that IFN-γ-producing CD4 T cells are not necessary. Interleukin 17A (IL-17A) also contributed to gastritis, but to a lesser extent than IFN-γ. Tumor necrosis factor alpha (TNF-α) and IL-17F were also elevated in association with disease. These results indicate that while H. pylori-specific CD4(+) T cells and IFN-γ are both essential for induction of gastritis due to H. pylori, IFN-γ production by T cells is not essential. It is likely that other proinflammatory cytokines, such as IL-17F and TNF-α, shown to be elevated in this model, also contribute to the induction of disease. We suggest that gastritis due to H. pylori is associated with loss of immunoregulation and alteration of several cytokines and cell subsets and cannot be attributed to a single immune pathway.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Female
  • Gastritis / immunology
  • Gastritis / microbiology*
  • Gene Expression Regulation / physiology
  • Helicobacter Infections / immunology*
  • Helicobacter Infections / microbiology
  • Helicobacter pylori*
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, SCID
  • T-Lymphocyte Subsets / physiology*

Substances

  • DNA-Binding Proteins
  • Interleukin-17
  • Rag2 protein, mouse
  • Interferon-gamma