Survival of Intrastriatal Xenografts of Ventral Mesencephalic Dopamine Neurons from MHC-Deficient Mice to Adult Rats

Autor: Duan, Wei-Ming, Westerman, Marcus, Flores, Tina, Low, Walter C.
Zdroj: Experimental Neurology; January 2001, Vol. 167 Issue: 1 p108-117, 10p
Abstrakt: 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.
Databáze: Supplemental Index