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

Abstract

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.