Mucosal FOXP3-expressing CD4+ CD25high regulatory T cells in Helicobacter pylori-infected patients.
Helicobacter pylori chronically colonizes the stomach and duodenum and causes peptic ulcers or gastric adenocarcinoma in 10 to 20% of infected individuals. We hypothesize that the inability of patients to clear H. pylori infections is a consequence of active suppression of the immune response. Here we show that H. pylori-infected individuals have increased frequencies of CD4(+) CD25(high) T cells in both the stomach and duodenal mucosa compared to uninfected controls. These cells have the phenotype of regulatory T cells, as they express FOXP3, a key gene for the development and function of regulatory T cells, as well as high levels of the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) protein. In contrast, mucosal CD4(+) CD25(low) and CD4(+) CD25(-) cells express little FOXP3 mRNA and low levels of the CTLA-4 protein. Mucosal CD4(+) CD25(high) T cells are present in individuals with asymptomatic H. pylori infections as well as in duodenal ulcer patients. The frequencies of CD4(+) CD25(high) cells are also increased in the stomachs of H. pylori-infected patients with gastric adenocarcinoma, particularly in cancer-affected tissues. These findings suggest that regulatory T cells may suppress mucosal immune responses and thereby contribute to the persistence of H. pylori infections.
Lundgren
Anna
A
Dept. of Medical Microbiology and Immunology, Göteborg University, Box 435, 405 30 Göteborg, Sweden. anna.lundgren@microbio.gu.se
Strömberg
Erika
E
Sjöling
Asa
A
Lindholm
Catharina
C
Enarsson
Karin
K
Edebo
Anders
A
Johnsson
Erik
E
Suri-Payer
Elisabeth
E
Larsson
Pia
P
Rudin
Anna
A
Svennerholm
Ann-Mari
AM
Lundin
B Samuel
BS
D000230:Adenocarcinoma / Q000276:immunology; D000328:Adult; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D060908:CTLA-4 Antigen; D004268:DNA-Binding Proteins / Q000235:genetics*; D004381:Duodenal Ulcer / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors; D005753:Gastric Mucosa / Q000276:immunology*; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D013274:Stomach Neoplasms / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015704:CD4 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015375:Receptors, Interleukin-2