title: A liver tolerates a portal antigen by generating CD11c+ cells, which select Fas ligand+ Th2 cells via apoptosis.
abstract: Administration of an antigen (Ag) per oral route leads to apoptosis of Ag-specific CD4(+) T cells and to development of Th2 cells expressing Fas ligand (FasL) in the liver. We determined whether presentation of an ingested Ag in the liver alone was enough to select these FasL(+)Th2 cells and explored how this selection was achieved in the liver. Ovalbumin (OVA) administered orally was colocalized with class II(+) cells in the periportal and parenchymal area of the liver. On coculture with naive OVA-specific CD4(+) T cells, hepatic CD11c(+) cells from mice fed OVA generated Ag-specific Th2 cells. This was achieved by apoptosis of CD4(+) T cells, decrease of interleukin 12 (IL-12) secretion, and increase of IL-18 secretion by the CD11c(+) cells. Addition of IL-12 to this coculture prevented apoptosis of the CD4(+) T cells, which was associated with up-modulation of IL-2 receptor beta chain expression. Administration of IL-12 to mice fed OVA prevented apoptosis of OVA-specific CD4(+) T cells in the liver. Moreover, adoptive transfer of hepatic CD11c(+) cells from mice fed OVA together with OVA-specific CD4(+) T cells led to development of Th2 cells as well as apoptosis of the transferred CD4(+) T cells in the lymph nodes of the recipient mice on immunization with OVA. In conclusion, presentation of an ingested Ag by hepatic CD11c(+) cells selects Th2 cells resistant to apoptosis in the liver, which is mediated in part by down-regulation of IL-12 secretion by the former cells.
authors.affiliation: Department of Clinical Bioregulatory Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Watanabe
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Katsukura
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Shirai
authors.forename: Masashi
authors.initials: M
authors.lastname: Yamori
authors.forename: Toshiki
authors.initials: T
authors.lastname: Nishi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Wakatsuki
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D039521:CD11c Antigen / Q000032:analysis*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D007108:Immune Tolerance / Q000276:immunology; D007114:Immunization; D018664:Interleukin-12 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000032:analysis*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D018418:Th2 Cells / Q000737:chemistry* / Q000166:cytology* / Q000378:metabolism
chemical_list: D039521:CD11c Antigen; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D020382:Interleukin-18; D008562:Membrane Glycoproteins; D018664:Interleukin-12; D010047:Ovalbumin