Abstract

During H. pylori infection, T cells are recruited to the gastric mucosa, but the host response is unable to clear the infection. We have previously shown that during infection H. pylori induces B7-H1 on the gastric epithelium, and interacting T cells are thus anegized. Recently, T regulatory cells (Treg) with a CD4+ CD25high FoxP3+ phenotype were found at an increased frequency in the H. pylori-infected gastric mucosa. Since B7-H1 promotes T cell anergy during H. pylori infection and Treg cells are present in the infected gastric mucosa, we hypothesized that B7-H1 expression by gastric epithelial cells duringH. pyloriinfection promotes development of T regulatory cells. In order to investigate this, we examined by flow cytometry the induction of the Treg phenotype when naïve T cells were incubated with H. pylori-exposed gastric epithelial cells. The number of CD4+CD25+FoxP3+ cells increased together with the production of IL-10 and TGF-β in the cultures. The frequency of Treg cells along with IL-10 and TGF-β production was markedly decreased when B7-H1 was blocked with monoclonal antibodies. The function of these Treg cells was investigated by sorting them for use in co-cultures with activated T cells, which effectively decreased proliferation of the activated T cells. B7-H1 may thereby play a crucial role in the development of CD4+CD25+FoxP3+ Treg cells and the inadequate T cell response leading to chronic infection.

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