title: Role of the liver in determining alloimmune response in vitro following donor-specific spleen cell injection.
abstract: The aim of our study was to investigate the allogeneic influence inside and outside the liver in vitro following donor-specific cell injection (DSI). DA rats (RT1a) were used as donors and WS rats (RT1k) as recipients. WS were sensitized with DA spleen cells, followed 24h later by total hepatectomy. The liver was transplanted into another WS (sensitized liver-grafted; SL-Grafted). The hepatectomized WS underwent liver transplantation from a naive WS (sensitized liver-removed; SL-Removed). Alloantigens accumulated in the liver in SL-Grafted and in the extrahepatic tissue/organ(s) in SL-Removed. DA hearts were transplanted 10days after antigen administration. To analyze the immune responses, we measured Th1/Th2 cytokine profiles, and perforin mRNA in various organs, allogeneic mixed lymphocyte reaction (MLR), and donor-specific immunoglobulin. Th1 cytokine levels in the liver of SL-Grafted and in spleen of SL-Removed were highly and rapidly upregulated but decreased thereafter. IFN-gamma and perforin mRNAs were significantly higher in SL-Grafted and lower in SL-Removed. MLR was significantly higher in SL-Grafted than SL-Removed and controls. There was no significant difference in the donor-specific immunoglobulin level. Our findings suggest that liver and other organs may behave differently to alloantigen, suggesting the importance of an early Th1 reaction in the liver and spleen.
authors.affiliation: Department of Surgery, Graduate School of Medicine Osaka University, Osaka 565-0871, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Okuyama
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagano
authors.forename: Shogo
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Li
authors.initials: L
authors.lastname: He
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ota
authors.forename: Junzo
authors.initials: J
authors.lastname: Shimizu
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takeda
authors.forename: Shigeru
authors.initials: S
authors.lastname: Masrubashi
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Eguchi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tanemuea
authors.forename: Keizo
authors.initials: K
authors.lastname: Dono
authors.forename: Masato
authors.initials: M
authors.lastname: Sakon
authors.forename: Koji
authors.initials: K
authors.lastname: Umeshita
authors.forename: Mitsukazu
authors.initials: M
authors.lastname: Gotoh
authors.forename: Morito
authors.initials: M
authors.lastname: Monden
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D017690:Cell Transplantation; D016207:Cytokines / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D016027:Heart Transplantation; D056747:Immunomodulation; D007519:Isoantigens / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016031:Liver Transplantation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D054353:Perforin / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D016207:Cytokines; D007519:Isoantigens; D054353:Perforin