title: Liver sinusoidal endothelial cells that endocytose allogeneic cells suppress T cells with indirect allospecificity.
abstract: A portal venous injection of allogeneic donor cells is known to prolong the survival of subsequently transplanted allografts. In this study, we investigated the role of liver sinusoidal endothelial cells (LSECs) in immunosuppressive effects induced by a portal injection of allogeneic cells on T cells with indirect allospecificity. To eliminate the direct CD4+ T cell response, C57BL/6 (B6) MHC class II-deficient C2tatm1Ccum (C2D) mice were used as donors. After portal injection of irradiated B6 C2D splenocytes into BALB/c mice, the host LSECs that endocytosed the irradiated allogeneic splenocytes showed enhanced expression of MHC class II molecules, CD80, and Fas ligand (FasL). Due to transmigration across the LSECs from BALB/c mice treated with a portal injection of B6 C2D splenocytes, the naive BALB/c CD4+ T cells lost their responsiveness to stimulus of BALB/c splenic APCs that endocytose donor-type B6 C2D alloantigens, while maintaining a normal response to stimulus of BALB/c splenic APCs that endocytose third-party C3H alloantigens. Similar results were not observed for naive BALB/c CD4+ T cells that transmigrated across the LSECs from BALB/c FasL-deficient mice treated with a portal injection of B6 C2D splenocytes. Adaptive transfer of BALB/c LSECs that had endocytosed B6 C2D splenocytes into BALB/c mice via the portal vein prolonged the survival of subsequently transplanted B6 C2D hearts; however, a similar effect was not observed for BALB/c FasL-deficient LSECs. These findings indicate that LSECs that had endocytosed allogeneic splenocytes have immunosuppressive effects on T cells with indirect allospecificity, at least partially via the Fas/FasL pathway.
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: Daisuke
authors.initials: D
authors.lastname: Tokita
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shishida
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohdan
authors.forename: Takashi
authors.initials: T
authors.lastname: Onoe
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: Hiroshi
authors.initials: H
authors.lastname: Mitsuta
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ide
authors.forename: Koji
authors.initials: K
authors.lastname: Arihiro
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Asahara
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D004705:Endocytosis / Q000276:immunology*; D042783:Endothelial Cells / Q000166:cytology* / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D016027:Heart Transplantation; D007108:Immune Tolerance; D007519:Isoantigens / Q000235:genetics / Q000276:immunology*; D008099:Liver / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*
chemical_list: D007519:Isoantigens