Survival of intrastriatal xenografts of ventral mesencephalic dopamine neurons from MHC-deficient mice to adult rats.
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.
Duan
W M
WM
Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
Westerman
M
M
Flores
T
T
Low
W C
WC
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
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D016177:Macrophage-1 Antigen; D016572:Cyclosporine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine