title: Hepatic CCR7lowCD62LlowCD45RClow allograft dendritic cells migrate to the splenic red pulp in immunologically unresponsive rats.
abstract: Donor dendritic cells (DC) migrate into the recipient spleen after hepatic transplantation. Immunological unresponsiveness to rat hepatic allografts can be induced by prior donor-specific blood transfusion (DST). We investigated homing receptor phenotype and splenic distribution of donor DC after allografting and DST. Immunostaining revealed OX62+ cells in the splenic red pulp of animals receiving pre-transplant DST but only in the white pulp of untreated animals. Most OX62 cells were positive for OX76. There were two subsets of DC in the spleen, CD45RChighOX62+ and CD45RClowOX62+ cells. RT-PCR revealed that CD45RClowOX62+ cells expressed interleukin (IL)-10, while CD45RChighOX62+ cells expressed IL-2 and low levels of IL-10 mRNA. CD45RChighOX62+ cells strongly expressed CCR5 and CCR7, compared with weak expression in CD45RClowOX62+ cells. The Epstein-Barr virus-induced molecule 1 (EBI-1) ligand chemokine (ELC/MIP3beta) was expressed mainly within the splenic white pulp. Mucosal vascular addressin-cell adhesion molecule-1 (MAdCAM-1) was expressed in the marginal zone and white pulp, but expression of splenic MAdCAM-1 was down-regulated in DST-treated animals. L-selectin (CD62L), the ligand for MAdCAM-1, was strongly expressed on CD45RChighOX62+ cells but not on CD45RClowOX62+ cells. In conclusion, differential splenic migration of CCR5lowCCR7lowCD62Llow CD45RClow DC expressing Th2-type cytokines is associated with immunological unresponsiveness to rat hepatic allografts.
authors.affiliation: Department of Surgery II Kumamoto University Medical School, Kumamoto, Japan. furu-p74@zephyr.dti.ne.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Furuhashi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Feng-Shan
authors.initials: FS
authors.lastname: Wang
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Uchino
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Okabe
authors.forename: Hajime
authors.initials: H
authors.lastname: Ohshiro
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kihara
authors.forename: Shinwa
authors.initials: S
authors.lastname: Yamada
authors.forename: Katsutaka
authors.initials: K
authors.lastname: Mori
authors.forename: Michio
authors.initials: M
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000276:immunology; D001803:Blood Transfusion; D002465:Cell Movement / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D007136:Immunoglobulins / Q000276:immunology; D019041:L-Selectin / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000276:immunology; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D023421:Models, Animal; D009088:Mucoproteins / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D019713:Receptors, CCR5 / Q000276:immunology; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D013154:Spleen / Q000276:immunology*; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D000943:Antigens, Differentiation; C515372:Ccr7 protein, rat; D007136:Immunoglobulins; C504268:Madcam1 protein, rat; D009088:Mucoproteins; C459465:OX-62 antigen, rat; D019713:Receptors, CCR5; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D016201:Receptors, Lymphocyte Homing; D019041:L-Selectin; D017493:Leukocyte Common Antigens