Hepatic CCR7lowCD62LlowCD45RClow allograft dendritic cells migrate to the splenic red pulp in immunologically unresponsive 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, CD45RC high OX62 + and CD45RC low OX62 + cells. RT-PCR revealed that CD45RC low OX62 + cells expressed interleukin (IL)-10, while CD45RC high OX62 + cells expressed IL-2 and low levels of IL-10 mRNA. CD45RC high OX62 + cells strongly expressed CCR5 and CCR7, compared with weak expression in CD45RC low OX62 + 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 CD45RC high OX62 + cells but not on CD45RC low OX62 + cells. In conclusion, differential splenic migration of CCR5 low CCR7 low CD62L low CD45RC low DC expressing Th2-type cytokines is associated with immunological unresponsiveness to rat hepatic allografts.