FOXP3-expressing CD4(+) T-cell numbers increase in areas of duodenal gastric metaplasia and are associated to CD4(+) T-cell aggregates in the duodenum of Helicobacter pylori-infected duodenal ulcer patients.
BACKGROUND
We have previously demonstrated that Helicobacter pylori infection is associated with an increased number of CD4(+)CD25(high) regulatory T cells in the gastric and duodenal mucosa. In this study, we determined the number and localization of CD4(+) cells expressing the regulatory T-cell-specific transcription factor FOXP3 in the antrum and duodenum of duodenal ulcer patients, asymptomatic carriers, and uninfected individuals. We also determined gene expression levels of FOXP3 as well as anti- and proinflammatory cytokines before and after H. pylori eradication.


METHODS
Cellular FOXP3 expression was studied by immunofluorescence and flow cytometry, and transcription levels of FOXP3, interleukin (IL)-10, transforming growth factor-beta, CD4, and interferon-gamma were analyzed by real-time reverse transcription-polymerase chain reaction.


RESULTS
We found an increased (6-fold) frequency of CD4(+)FOXP3(+) T cells in H. pylori-infected gastric mucosa; interestingly 26% of these cells did not co-express CD25. The increase of FOXP3-expressing T cells in the antrum of infected individuals was dependent on the presence of H. pylori, since eradication therapy resulted in 4-fold lower levels of FOXP3 and IL-10 mRNA in the antrum. Furthermore, higher numbers of CD4(+)FOXP3(+) T cells were found in areas of duodenal gastric metaplasia in the duodenum of duodenal ulcer patients compared to duodenal gastric metaplasia of asymptomatic individuals and healthy mucosa in both patient groups. In duodenal ulcer patients, the CD4(+)FOXP3(+) T cells were more highly associated to aggregates in the duodenal mucosa.


CONCLUSIONS
The numbers of CD4(+)FOXP3(+) T cells are increased and localized in CD4(+) T-cell aggregates in areas of duodenal gastric metaplasia in duodenal ulcer patients.
Kindlund
Bert
B
Department of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg and Mucosal Immunobiology and Vaccine Center, Gothenburg, Sweden. bert.kindlund@microbio.gu.se
Sjöling
Asa
A
Hansson
Malin
M
Edebo
Anders
A
Hansson
Lars-Erik
LE
Sjövall
Henrik
H
Svennerholm
Ann-Mari
AM
Lundin
B Samuel
BS
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D004381:Duodenal Ulcer / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000032:analysis*; D005753:Gastric Mucosa / Q000276:immunology / Q000473:pathology; D020869:Gene Expression Profiling; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D008297:Male; D008679:Metaplasia / Q000276:immunology* / Q000473:pathology; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D055815:Young Adult
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma