Naturally occurring regulatory T cells (CD4+, CD25high, FOXP3+) in the antrum and cardia are associated with higher H. pylori colonization and increased gene expression of TGF-beta1.
BACKGROUND
Helicobacter pylori causes gastric inflammation. Despite the induction of H. pylori-specific B- and T cells, the immune response is not sufficient to clear the infection. Regulatory T cells (Treg cells) suppress the activation and proliferation of antigen-specific T cells and mediate immunologic tolerance. FOXP3 was shown to be expressed in a subset of Treg cells known as 'naturally occurring Treg cells'. These cells have not been sufficiently studied in context to H. pylori-induced inflammation in human gastric mucosa.


METHODS
The study included 76 patients stratified according to the presence of H. pylori. Gene expression levels of FOXP3, transforming growth factor (TGF)-beta1, and interleukin-10 were analyzed by quantitative real-time polymerase chain reaction in biopsies from gastric antrum, corpus, and cardia. FOXP3 expression was also analyzed by immunohistochemistry. Differences in expression levels were analyzed by comprehensive statistical analyses and correlated with clinical and histomorphologic parameters.


RESULTS
H. pylori-positive patients revealed a 19- to 25-fold induction of FOXP3 transcript levels in antrum and cardia (p < .02). FOXP3 transcript levels correlated positively with inflammation (p < .04) and TGF-beta1 transcript levels (p < .001). Furthermore, a positive correlation between FOXP3(+) Treg cells and H. pylori colonization was demonstrated.


CONCLUSIONS
This study demonstrates that H. pylori-induced gastritis is associated with a recruitment of naturally occurring FOXP3(+) Treg cells that correlates with the degree of bacterial colonization and mucosal TGF-beta1 expression. Together, these data support the hypothesis that naturally FOXP3(+) Treg cells play a role in the lifelong persistence of H. pylori infection in humans.
Kandulski
Arne
A
Department of Gastroenterology, Hepatology and Infectious Diseases, Leipziger Str. 44, D-39120, Germany.
Wex
Thomas
T
Kuester
Doerthe
D
Peitz
Ulrich
U
Gebert
Ingrid
I
Roessner
Albert
A
Malfertheiner
Peter
P
D000328:Adult; D000368:Aged; D015704:CD4 Antigens / Q000276:immunology; D002299:Cardia / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005756:Gastritis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000254:growth & development*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011706:Pyloric Antrum / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D015704:CD4 Antigens; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D053773:Transforming Growth Factor beta1