CONTRIBUTIONS OF DONOR AND HOST BLOOD-VESSELS IN CNS ALLOGRAFTS

The contributions of blood vessels in various transplantation paradigm s of solid CNS tissue or cell suspension allografts placed into adult host brains were investigated immunohistochemically using the PVG-RT1( C) and PVG-RT1(U) inbred rat strains and a panel of highly specific mo noclonal antibodies. The monoclonal antibodies included OX-27 and U9F4 against major histocompatibility complex (MHC) class I antigens of th e PVG-RT1(C) and PVG-RT1(U) rats, respectively; OX-26 against the rat transferrin receptor located on blood-brain barrier (BBB) endothelia; and OX-7 against rat neuronal Thy 1.1 for evaluating graft survival, O ur study is the first to address the immunogenicity of blood vessels i n surviving CNS allografts. Solid fetal or neonatal PVG-RT1(C) cortex was grafted into the third or lateral cerebral ventricle or caudate/pu tamen of PVG-RT1(U) adult hosts for 30 days to 7 months. All allograft s expressed demonstrable Thy 1.1 immunoreactivity with OX-7 antibody a nd appeared well-vascularized with blood vessels that immunostained wi th the OX-26 antibody against the transferrin receptor For the most pa rt, the allografts were supplied sparsely with donor (PVG-RT1(C)) MHC class I-positive (OX-27) blood vessels clustered in pockets. Donor MHC class I-positive vessels entered the host brain only from allografts in the third ventricle; these vessels were restricted to the host medi an eminence and no longer immunostained with OX-26 for the transferrin receptor (normally the median eminence is supplied with non-BBB vesse ls that do not possess the transferrin receptor and do not stain with OX-26). In host brains harboring a third ventricle allograft, host MHC class I-positive vessels immunostained with the U9F4 antibody were ev ident throughout the host CNS, including the median eminence, and thro ughout the allografts excluding sites inhabited by donor PVG-RT1(C) ve ssels, Cell suspension neural allografts (donor PVG-RT1(C)) placed wit hin the brain parenchyma of PVG-RT1(U) hosts revealed no significant d ifferences in vascular contributions between donor and host when compa red to results obtained from solid CNS allografts. A unique immunohist ochemical approach of introducing ascites fluid OX-27 as the primary a ntibody intravenously to the PVG-RT1(U) host demonstrated that in dono r PVG-RT1(C) posterior pituitary allografts, donor and not host vessel s predominate and are restricted to the graft, Finally, blood vessels isolated from adult PVG-RT1(C) brains were mixed with solid fetal PVG- RT1(U) cortical tissue and grafted into the brain parenchyma of adult PVG-RT1(U) hosts. Immunostaining with OX-27 antibody against MHC class I of the PVG-RT1(C) rat strain disclosed that the PVG-RT1(C) blood ve ssels survived and were confined to the PVG-RT1(U) syngeneic graft, Th e results suggest that blood vessels supplying CNS allografts placed w ithin the host brain are predominantly of host origin; surviving donor vessels are restricted to the allograft with rare exceptions, which m ay be dictated by the type of neural allograft and the host CNS site r eceiving the allograft. The survival of isolated allogeneic CNS blood vessels grafted into the host brain suggests that such blood vessels c an present an endothelial genotype and phenotype different from those of host vessels indigenous to the CNS site receiving the allogeneic ve ssel graft, This finding may have implications in the circumvention of the blood-brain fluid barriers for the CNS delivery of blood-borne th erapeutics. (C) 1996 Academic Press, Inc.