Differential splenic migration of dendritic cells after immunologic unresponsiveness in rat hepatic allografts induced by pretransplant donor-specific transfusion

Background. Donor dendritic cells migrate into the recipient spleen after h epatic transplantation. We previously reported that immunologic unresponsiv eness to rat hepatic allografts can be induced by prior donor-specific bloo d 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 (RT1B(a)) (OX-76) antibodies. The phen otype of dendritic cells was determined with antibodies to CD45RC, CD62L, a nd 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 an alyzed by reverse transcription polymerase chain reaction (RT-PCR). Results. Pretransplant DST significantly prolonged rat hepatic allograft su rvival. Immunostaining revealed OX76(+)/OX-62(+) cells in the splenic red p ulp of animals receiving pretransplant DST and in the white pulp of untreat ed animals after transplantation. The ratio of splenic CD45RC(-) OX-62(+) c ells to CD45RC(+) OX62(+) 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 gamma (IFN-gam ma). Conclusion. Differential splenic migration of CD45RC(-) dendritic cells is associated with immunologic unresponsiveness to rat hepatic allografts. (C) 2001 Academic Press.