title: Repeating intraportal donor-specific transfusion may induce tolerance following adult living-related donor liver transplantation.
abstract: OBJECTIVE
  Oral or portal administration of allogeneic antigens downregulates the alloimmune response and prolongs graft survival following organ transplantation. However, the effect of donor-specific transfusion via the portal vein has been reported in rodent models, but has not been reported in human cases. We investigated whether donor-specific transfusion via the portal vein would bring up the clinical and immunological benefits in living-related donor liver transplantation.
  
  
  METHODS
  Eighteen patients who underwent living-related donor liver transplantation from March 1999 to December 2001, were investigated. Seven patients were given the Tac + steroid regimen (IP(-) group: n = 7, mean age 54 +/- 9 yo). Eleven patients had postoperative repeated donor specific transfusion performed via a portal venous catheter inserted from vena colica media besides from the Tac + steroid (IP(+) group: n = 11, mean age 45 +/- 15 yo). The clinical effects of the reduction of immunosuppression and the rejection, and the immunological analysis were studied in the two groups.
  
  
  RESULTS
  Total amount of methylprednisolone and prednisolone within one month in the IP(+) group was smaller than that in the IP(-) group with statistical significance. Amount of Tac within one month and Trough level of Tac was statistically smaller in the IP(+) group than that in the IP(-) group. Minimum dose of Tac in the IP(+) group was clearly smaller than that in the IP(-) group with statistical significance. The frequency of acute cellular rejection within one month and after one month or total frequency of acute cellular rejection in the IP(+) group tended to be less than that in the IP(-) group. Macrochimerism of donor type CD56+ T cells in a graft were confirmed in patients with donor-specific transfusion via the portal vein. Conversely recipient type CD56+ T cells increased in the graft liver in patients without donor-specific transfusion. IL-10 production of the donor-specific transfusion(+) group was higher than that of the donor-specific transfusion(-) group on day 1 after living-related donor liver transplantation.
  
  
  CONCLUSIONS
  The repeated donor-specific transfusion via the portal vein has brought the rapid reduction of immunosuppressants. Donor type natural killer T cells especially CD56+ T cells, may induce tolerance by Veto mechanism and anti-idiotype network mechanism. These benefits might introduce more advantages in frequency of complications and cost of transplantation.
authors.affiliation: Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences 1-757 Asahimachi-dori, Niigata City, Niigata 951-8510, Japan. kanishok@med.niigata-u.ac.jp
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Sato
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ichida
authors.forename: Hisami
authors.initials: H
authors.lastname: Watanabe
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Oya
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakatsuka
authors.forename: Takashi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Takaoki
authors.initials: T
authors.lastname: Watanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kameyama
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Hatakeyama
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001803:Blood Transfusion; D018959:CD57 Antigens / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000939:Epitopes / Q000008:administration & dosage* / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007519:Isoantigens / Q000008:administration & dosage* / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D016031:Liver Transplantation / Q000276:immunology*; D019520:Living Donors; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D011169:Portal Vein; D011239:Prednisolone / Q000008:administration & dosage; D016559:Tacrolimus / Q000008:administration & dosage
chemical_list: D018959:CD57 Antigens; D000939:Epitopes; D007166:Immunosuppressive Agents; D007519:Isoantigens; D011239:Prednisolone; D016559:Tacrolimus; D008775:Methylprednisolone