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Infection and Immunity, January 2005, p. 523-531, Vol. 73, No. 1
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.1.523-531.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Mucosal FOXP3-Expressing CD4⁺ CD25^high Regulatory T Cells in Helicobacter pylori-Infected Patients

Department of Medical Microbiology and Immunology and Göteborg University Vaccine Research Institute (GUVAX),¹ Department of Surgery,² Department of Rheumatolology and Inflammation Research, Göteborg University, Göteborg, Sweden,⁴ Department of Immunogenetics, German Cancer Research Center, Heidelberg, Germany³

Received 6 July 2004/ Returned for modification 26 August 2004/ Accepted 14 September 2004

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.

Editor: A. D. O'Brien

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