title: Liver sinusoidal endothelial cells have a capacity for inducing nonresponsiveness of T cells across major histocompatibility complex barriers.
abstract: Livers transplanted across major histocompatibility complex (MHC) barriers in mice are normally accepted without recipient immune suppression. To identify the cell type that contributes to induction of such a tolerance state, we established an allogeneic mixed hepatic constituent cell-lymphocyte reaction (MHLR) assay. Hepatic constituent cells were isolated from C57BL/6 (B6) and Balb/c mice as stimulators, and splenocytes were isolated from B6 mice as responders. Irradiated hepatic constituent cells were co-cultured with fluorescent dye (CFSE)-labeled B6 splenocytes. In the allogeneic MHLR using either whole hepatic constituent cells or parenchymal hepatocytes as stimulators, a lack of T-cell proliferation was observed. Only when CD105(+) cells, which are exclusively liver sinusoidal endothelial cells (LSECs), were depleted from hepatic constituent cell stimulators, the MHLR resulted in marked proliferation of both allo-reactive CD4(+) and CD8(+) T cells. These results indicate that CD105(+) LSECs have the capacity to induce nonresponsiveness of T cells across MHC barriers.
authors.affiliation: Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Onoe
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohdan
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tokita
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Hara
authors.forename: Yuka
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Kohei
authors.initials: K
authors.lastname: Ishiyama
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Asahara
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000276:immunology; D005260:Female; D022781:Hepatocytes / Q000276:immunology*; D007108:Immune Tolerance; D066298:In Vitro Techniques; D007519:Isoantigens; D016031:Liver Transplantation / Q000276:immunology; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D007519:Isoantigens