title: Survival of intrastriatal xenografts of ventral mesencephalic dopamine neurons from MHC-deficient mice to adult rats.
abstract: Previous studies of neural xenografts have used immunosuppressive agents to prevent graft rejection. In the present study we have examined the survival of mouse dopamine neurons lacking either MHC class I or MHC class II molecules transplanted into rat brains and the host immune and inflammatory responses against the xenografts. Survival of neural grafts was immunocytochemically determined at 4 days, 2 weeks, and 6 weeks after transplantation by counting tyrosine hydroxylase (TH)-positive cells in the graft areas. In addition, the host immune and inflammatory responses against neural xenografts were evaluated by semiquantitatively rating MHC class I and class II antigen expression, accumulation of macrophages and activated microglia, and infiltration of CD4- and CD8-positive T-lymphocytes. For the negative controls, the mean number of TH-positive cells in rats that received wild-type mouse tissue progressively decreased at various time periods following transplantation. In contrast, intrastriatal grafting of either MHC class I or MHC class II antigen-depleted neural xenografts resulted in a prolonged survival and were comparable to cyclosporin A-treated rats that had received wild-type mouse tissue. These results indicate that genetically modified donor tissue lacking MHC molecules can be used to prevent neural xenograft rejection.
authors.affiliation: Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: Duan
authors.forename: M
authors.initials: M
authors.lastname: Westerman
authors.forename: T
authors.initials: T
authors.lastname: Flores
authors.forename: W C
authors.initials: WC
authors.lastname: Low
mesh_terms: D000818:Animals; D016380:Brain Tissue Transplantation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D003342:Corpus Striatum / Q000166:cytology* / Q000601:surgery; D016572:Cyclosporine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D016332:Fetal Tissue Transplantation; D006085:Graft Survival / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology / Q000637:transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014183:Transplantation, Heterologous / Q000276:immunology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D016177:Macrophage-1 Antigen; D016572:Cyclosporine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine