Differential Splenic Migration of Dendritic Cells after Immunologic Unresponsiveness in Rat Hepatic Allografts Induced by Pretransplant Donor-Specific Transfusion

Abstract

Background. Donor dendritic cells migrate into the recipient spleen after hepatic transplantation. We previously reported that immunologic unresponsiveness to rat hepatic allografts can be induced by prior donor-specific blood transfusion (DST). We investigated the phenotype and splenic distribution of donor dendritic cells after allografting and DST.Methods. Donor dendritic cells were identified with anti-rat dendritic cell (OX-62) and anti-donor class II MHC (RT1Ba) (OX-76) antibodies. The phenotype of dendritic cells was determined with antibodies to CD45RC, CD62L, and the maturation markers CD80 (B7-1) and CD86 (B7-2). The cytokine profile of sorted CD45RC+ OX-62+ and CD45RC− OX-62+ dendritic cells was analyzed by reverse transcription polymerase chain reaction (RT-PCR).Results. Pretransplant DST significantly prolonged rat hepatic allograft survival. Immunostaining revealed OX76+/OX-62+ cells in the splenic red pulp of animals receiving pretransplant DST and in the white pulp of untreated animals after transplantation. The ratio of splenic CD45RC− OX-62+ cells to CD45RC+ OX-62+ cells was significantly higher in DST recipients than in untreated animals. CD62L, CD80, and CD86 were lower on CD45RC− OX-62+ than CD45RC+ OX-62+ cells. RT-PCR revealed that sorted CD45RC− OX-62+ cells expressed interleukin (IL)-4 and IL-10. In contrast, sorted CD45RC+ OX-62+ cells expressed only IL-2 and interferon γ (IFN-γ).Conclusion. Differential splenic migration of CD45RC− dendritic cells is associated with immunologic unresponsiveness to rat hepatic allografts.