Helicobacter pylori gastritis in children is associated with a regulatory T-cell response.
OBJECTIVE
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.
Harris
Paul R
PR
Department of Pediatrics, Pontificia Universidad Católica de Chile and Hospital Dr. Sótero del Río, Santiago, Chile.
Wright
Shelton W
SW
Serrano
Carolina
C
Riera
Francisca
F
Duarte
Ignacio
I
Torres
Javiera
J
Peña
Alfredo
A
Rollán
Antonio
A
Viviani
Paola
P
Guiraldes
Ernesto
E
Schmitz
Julia M
JM
Lorenz
Robin G
RG
Novak
Lea
L
Smythies
Lesley E
LE
Smith
Phillip D
PD
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000473:pathology; D049109:Cell Proliferation; D002648:Child; D002677:Chile; D015536:Down-Regulation; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005756:Gastritis / Q000209:etiology / Q000276:immunology* / Q000821:virology*; D016481:Helicobacter Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000473:pathology* / Q000502:physiology* / Q000821:virology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10