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Mucosal FOXP3-expressing CD4+ CD25high regulatory T cells in Helicobacter pylori-infected patients

Journal article
Authors Anna Lundgren
Erika Strömberg
Åsa Sjöling
Catharina Lindholm
Karin Enarsson
Anders Edebo
Erik Johnsson
Elisabeth Suri-Payer
Pia Larsson
Anna Rudin
Ann-Mari Svennerholm
Samuel B Lundin
Published in Infect Immun
Volume 73
Issue 1
Pages 523-31
Publication year 2005
Published at Institute of Internal Medicine, Dept of Rheumatology and Inflammation Research
Institute of Medical Microbiology/Immunology
Institute of Surgical Sciences, Department of Surgery
Pages 523-31
Language en
Links dx.doi.org/10.1128/IAI.73.1.523-531...
Keywords Adenocarcinoma/immunology, Adult, Antigens, CD, Antigens, CD4/*analysis, Antigens, Differentiation/analysis, CD4-Positive T-Lymphocytes/physiology, DNA-Binding Proteins/*genetics, Duodenal Ulcer/immunology, Female, Forkhead Transcription Factors, Gastric Mucosa/*immunology, Helicobacter Infections/*immunology, *Helicobacter pylori, Humans, Immunologic Memory, Male, Middle Aged, Receptors, Interleukin-2/*analysis, Stomach Neoplasms/immunology, T-Lymphocytes, Regulatory/*physiology
Subject categories Medical and Health Sciences

Abstract

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.

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