Helicobacter pylori-induced peptic ulcer disease is associated with inadequate regulatory T cell responses.
Gut
; 57(10): 1375-85, 2008 Oct.
Article
in En
| MEDLINE
| ID: mdl-18467372
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(+)CD25(hi)IL10(+) 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptic Ulcer
/
Stomach Neoplasms
/
CD4-Positive T-Lymphocytes
/
Helicobacter pylori
/
Helicobacter Infections
/
Gastric Mucosa
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Gut
Year:
2008
Document type:
Article
Affiliation country:
Reino Unido