Helicobacter pylori-induced peptic ulcer disease is associated with inadequate regulatory T cell responses.
OBJECTIVE
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.
Robinson
K
K
Institute of Infection, Immunity & Inflammation, University of Nottingham, Centre for Biomolecular Sciences, Nottingham, UK. karen.robinson@nottingham.ac.uk
Kenefeck
R
R
Pidgeon
E L
EL
Shakib
S
S
Patel
S
S
Polson
R J
RJ
Zaitoun
A M
AM
Atherton
J C
JC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D005260:Female; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000276:immunology* / Q000382:microbiology; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D010437:Peptic Ulcer / Q000276:immunology*; D016133:Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000276:immunology* / Q000382:microbiology