INDUCTION OF SPECIFIC TOLERANCE TO MHC-DISPARATE ALLOGRAFTS THROUGH GENETIC-ENGINEERING

The potential for induction of transplantation tolerance through genet ic engineering of allogeneic MHC genes is being studied in two animal models. The first system involves a congenic mouse strain combination differing by a single class I locus. Using a retroviral vector, cDNA e ncoding one allele of this locus was introduced into bone marrow of th e congenic partner strain, and the transduced bone marrow was used to reconstitute autologous animals. Skin-grafting data indicate that this reconstitution led to tolerance for the allelic products of this clas s I locus. The second system involves similar manipulations of miniatu re swine bone marrow, with the goal of inducing to tolerance to class II antigens, since these antigens have been shown to be of overwhelmin g importance in determining the fate of vascularized allografts in thi s model. In vitro data in a bone marrow culture system indicate that a n appropriate vector for this purpose has been produced.