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

Abstract

The purpose of the present study was to examine the effect of pretransplantation portal venous immunization with ultraviolet B (UVB)-treated donor spleen cells on neural xenograft transplantation. Cells from a murine catecholaminergic cell line derived from the B6/D2 F1 mouse, CATH.a, were used as a xenograft. Thirty hemiparkinsonian rats were divided into three different treatment groups. Group 1 received saline in the dopamine-denervated striatum; Group 2 received xenograft cells; and Group 3 received portal venous administration of UVB-irradiated B6/D2 F1 splenocytes 7 days before receiving xenograft cells. Xenograft function was determined by reviewing apomorphine-induced rotation at 2-week intervals, and xenograft survival was examined at 4 and 12 weeks after transplantation by immunohistochemical staining for murine tyrosine hydroxylase (THase). Rotational behavior was improved in both xenograft-transplanted groups (Groups 2 and 3); however, the animals in Group 3 displayed a significantly reduced rotational behavior compared with Group 2. In Group 2, many inflammatory cells and a few THase-positive cells were found at the graft sites 4 weeks after transplantation. In Group 3, however, a large number of THase-positive 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 animals. In Group 3 rats proliferation of spleen cells in a mixed lymphocyte reaction was suppressed in a donor-specific fashion. This work demonstrates improved neural xenograft survival and function by pretransplantation portal venous immunization with UVB-irradiated xenogeneic donor splenocytes. On the basis of these findings, the authors suggest the possibility of creating donor-specific immunological tolerance in the brain by administration of xenogeneic donor lymphocytes via the portal vein.