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- W2127036601 abstract "After ingestion, oral antigens distribute systemically and provoke T cell stimulation outside the gastrointestinal tract. Within the liver, scavenger liver sinusoidal endothelial cells (LSEC) eliminate blood-borne antigens and induce T cell tolerance. Here we investigated whether LSEC contribute to oral tolerance. Oral antigens were efficiently cross-presented on H-2Kb by LSEC to naive CD8 T cells. Cross-presentation efficiency in LSEC but not dendritic cells was increased by antigen-exposure to heat or low pH. Mechanistically, cross-presentation in LSEC requires endosomal maturation, involves hsc73 and proteasomal degradation. H-2Kb-restricted cross-presentation of oral antigens by LSEC in vivo induced CD8 T cell priming and led to development of CD8 T cell tolerance in two independent experimental systems. Adoptive transfer of LSEC from mice fed with antigen (ovalbumin) into RAG2–/– knockout mice, previously reconstituted with naive ovalbumin-specific CD8 T cells, prevented development of specific cytotoxicity and expression of IFN-γ in CD8 T cells. Using a new transgenic mouse line expressing H-2Kb only on endothelial cells, we have demonstrated that oral antigen administration leads to tolerance in H-2Kb-restricted CD8 T cells. Collectively, our data demonstrate a participation of the liver, in particular scavenger LSEC, in development of CD8 T cell tolerance towards oral antigens." @default.
- W2127036601 created "2016-06-24" @default.
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- W2127036601 date "2005-10-01" @default.
- W2127036601 modified "2023-10-14" @default.
- W2127036601 title "Cross-presentation of oral antigens by liver sinusoidal endothelial cells leads to CD8 T cell tolerance" @default.
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- W2127036601 doi "https://doi.org/10.1002/eji.200526034" @default.
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