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 surviva l of mouse dopamine neurons lacking either MHC class I or MHC class II mole cules transplanted into rat brains and the host immune and inflammatory res ponses against the xenografts. Survival of neural grafts was immunocytochem ically determined at 4 days, 2 weeks, and 6 weeks after transplantation by counting tyrosine hydroxylase (TH)-positive cells in the graft areas. In ad dition, the host immune and inflammatory responses against neural xenograft s were evaluated by semiquantitatively rating MHC class I and class II: ant igen expression, accumulation of macrophages and activated microglia, and i nfiltration of CD4- and CD8-positive T-lymphocytes. For the negative contro ls, the mean number of TH-positive cells in rats that received wild-type mo use tissue progressively decreased at various time periods following transp lantation. In contrast, intrastriatal grafting of either MHC class I or MHC class II antigen-depleted neural xenografts resulted in a prolonged surviv al 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 reject ion. (C) 2001 Academic Press.