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.
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 (T(reg)) 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 T(reg) cells with the intestinal homing phenotype.
Nagatani
Katsuya
K
Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Komagata
Yoshinori
Y
Asako
Kurumi
K
Takayama
Maki
M
Yamamoto
Kazuhiko
K
D000284:Administration, Oral; D000818:Animals; D017951:Antigen Presentation; D000941:Antigens; D002450:Cell Communication; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005456:Fluorescent Dyes; D051858:Forkhead Transcription Factors / Q000235:genetics; D015870:Gene Expression; D007108:Immune Tolerance; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010581:Peyer's Patches / Q000276:immunology*; D016133:Polymerase Chain Reaction; D054388:Receptors, CCR / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000941:Antigens; C119309:CC chemokine receptor 9; D005456:Fluorescent Dyes; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D054388:Receptors, CCR; D019707:Receptors, Chemokine; D010047:Ovalbumin