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Background: The pre-transplant administration of donor antigens to recipients is reported to prolong transplanted organ survival. We investigated the effect of pre-transplant intraportal administration of recipient blood on rat hepatic allograft survival., Materials and Methods: Male LEW (RT1l) and ACI (RT1a) rats were used as transplant recipients and donors, respectively. Before transplantation, donors were transfused with recipient blood. Experimental animals were divided into groups as follows: group I, no treatment; group II, pre-treatment with recipient blood via the penile vein 7 days before transplantation; group III, pre-treatment with recipient blood via the portal vein 5 days before transplantation; and group IV, pre-treatment with recipient blood via the portal vein 7 days before transplantation. Serum interferon (IFN)-gamma concentrations were measured post-operatively., Results: Animals in group I survived a mean of 10.1 +/- 0.7 days. The survival of groups II and III was 10.6 +/- 1.6 and 13.1 +/- 0.9 days, respectively. The survival rate in group IV was prolonged significantly to 33.7 +/- 2.6 days. Serum concentrations of IFN-gamma were increased significantly in group IV, as compared with group I. The ratio of OX76+CD4+ or OX76+CD8+ T cells to OX76-CD4+ or OX76-CD8+ T cells was greater in group IV, as compared group I. OX76+CD8+ T cells from hepatic allografts in group IV expressed IFN-gamma and interleukin (IL)-10, but not IL-2 mRNA. Apoptotic hepatic infiltrates were greater in group IV, as compared to group I., Conclusion: The cytokine profile of donor CD8+ T cells from allografts treated by the intraportal administration of recipient blood is associated with apoptosis of graft-infiltrating cells and the prolonged survival of hepatic allografts in rats.

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/MIP3β) 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. [Copyright &y& Elsevier]