Donor dendritic cells and recipient kupffer cells in the induction of donor-specific immune hyporesponsiveness

The aim of this study was to investigate the ability of portovenously admin istered donor antigens to induce immune hyporesponsiveness. Lewis (LEW, RT- 1(1)) rats received Brown Norway (BN, RT-1(n)) rat donor splenocytes, via e ither the portal vein (PV group) or the peripheral vein (IV group). The imm une responses of LEW rats, treated with either donor BN or third party Wist ar King A (WKA, RT-1(k)) splenocytes were established by the persistence of donor dendritic cells (DCs) in the host liver measured using fluorescence microscopy and flow cytometry and by the mixed lymphocyte reaction (MLR). T he effect of intravenous gadolinium chloride (GDCl(3)) on the blockade of K upffer cell function prior to portovenous administration of splenocytes was also assessed. The MLR response was strongly inhibited in a BN-restricted manner after portovenous administration of donor BN splenocytes, but not by venous nor by portovenous administration of WKA splenocytes. Immunosuppres sion was blocked by pretreatment with GDCl(3). The percentage of donor DCs in hepatic non-parenchymal cells (NPCs) was significantly higher in the PV group compared with the IV group. Treatment with GDCl(3) decreased the perc entage of donor DCs. In addition, cytotoxic T lymphocyte antigen 4(CTLA4/CD 152), which may function as an immune attenuator, was strongly stained, and B7 was weakly stained in recipient liver in the PV group compared with the IV group. These results suggest that both donor DCs and recipient Kupffer cells (self DCs) are involved in the induction of immune hyporesponsiveness by donor cells. This occurs via portovenous administration, in which a sig nal of the CTLA4-B7 pathway played an important part in inhibiting the inte raction of CD28 and its B7 ligands.