Repeating intraportal donor-specific transfusion may induce tolerance following adult living-related donor liver transplantation.

Background/aims: 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.

Methodology: 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.