Implantation of xenografts into the parkinsonian rat brain after portal venous administration of xenogeneic donor spleen cells

Object. The purpose of the present study was to examine the effect of pretr ansplantation portal venous immunization with ultraviolet B (UVB)-treated d onor spleen cells on neural xenograft transplantation. Methods. Cells from a murine catecholaminergic cell line derived from the B 6/D2 F1 mouse, CATH.a, were used as a xenograft. Thirty hemiparkinsonian ra ts were divided into three different treatment groups. Group 1 received sal ine in;he dopamine-denervated striatum; Group 2 received xenograft cells; a nd Group 3 received portal venous administration of UVB-irradiated B6/D2 F1 splenocytes 7 days before receiving xenograft cells. Xenograft function wa s determined by reviewing apomorphine-induced rotation at 2-week intervals, and xenograft survival was examined at 4 and 12 weeks after transplantatio n by immunohistochemical staining for murine tyrosine hydroxylase (THase). Rotational behavior was improved in both xenograft-transplanted groups (Gro ups 2 and 3); however, the animals in Group 3 displayed a significantly red uced rotational behavior compared with Group 2. In Group 2, many inflammato ry cells and a few THase-positive cells were found at the graft sites 4 wee ks after transplantation. In Group 3. however, a large number of THase-posi tive cells were found with few inflammatory cells. The THase-positive cells disappeared in the Group 2 rats at 12 weeks. but remained in Group 3 anima ls. In Group 3 rats proliferation of spleen cells in a mixed lymphocyte rea ction was suppressed in a donor-specific fashion. Conclusions. This work demonstrates improved neural xenograft survival and function by pretransplantation portal venous immunization with UVB-irradiat ed xenogeneic donor splenocytes. On the basis of these findings, the author s suggest the possibility of creating donor-specific immunological toleranc e in the brain by administration of xenogeneic donor lymphocytes via the po rtal vein.