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Antigen-specific regulatory T cells are detected in Peyer's patches after the interaction between T cells and dendritic cells loaded with orally administered antigen
Authors:Katsuya Nagatani  Yoshinori Komagata  Kurumi AsakoMaki Takayama  Kazuhiko Yamamoto
Institution:a Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
b Division of Rheumatology and Clinical Immunology, Jichi Medical University, Tochigi, Japan
c Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan
Abstract:Systemic immune tolerance is induced for orally administered antigen, and this phenomenon is called oral tolerance. However, the mechanism of oral tolerance has not been completely elucidated. It has been suggested that antigen presentation and generation of regulatory T cells in Peyer's patches (PPs) are important for induction of oral tolerance. Hence, we orally administered fluorescence-labelled antigen to mice and examined kinetics of the antigen and interaction between antigen-loaded dendritic cells and T cells. It was visualized that dendritic cells in PP rapidly take up antigen. We next transferred antigen-specific naïve T cells from T cell receptor transgenic mice and administered the antigen orally. Antigen-specific T cells accumulated in IFR in PP and DCs that have ingested antigen come in contact with antigen-specific T cells in IFR. The accumulated T cells were then collected and analyzed for the pattern of gene expression by real-time PCR, which revealed a gene expression pattern similar to that of FoxP3-positive regulatory T (Treg) cells. CCR9, an intestinal homing marker, was also strongly expressed. These results suggest that DCs that have captured oral antigens in PPs locally induce antigen-specific naïve T cells to differentiate into Treg cells with the intestinal homing phenotype.
Keywords:PPs  Peyer's patches  GALT  gut associated lymphoid tissue  Treg cell  regulatory T cell  DC  dendritic cell  OVAo  valbumin  SED  subepithelial dome  IFR  interfollicular region
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