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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+ CD25high Regulatory T Cells in Helicobacter pylori-Infected Patients

Anna Lundgren,1* Erika Strömberg,1 Åsa Sjöling,1 Catharina Lindholm,1 Karin Enarsson,1 Anders Edebo,2 Erik Johnsson,2 Elisabeth Suri-Payer,3 Pia Larsson,4 Anna Rudin,4 Ann-Mari Svennerholm,1 and B. Samuel Lundin1

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+ CD25high 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+ CD25low and CD4+ CD25– cells express little FOXP3 mRNA and low levels of the CTLA-4 protein. Mucosal CD4+ CD25high T cells are present in individuals with asymptomatic H. pylori infections as well as in duodenal ulcer patients. The frequencies of CD4+ CD25high 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.

* Corresponding author. Mailing address: Dept. of Medical Microbiology and Immunology, Göteborg University, Box 435, 405 30 Göteborg, Sweden. Phone: 46 31 7736213. Fax: 46 31 7736205. E-mail: anna.lundgren{at}microbio.gu.se.

Editor: A. D. O'Brien

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.



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