Induction of specific tolerance to MHC-disparate allografts through genetic engineering.

The potential for induction of transplantation tolerance through genetic 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 encoding one allele of this locus was introduced into bone marrow of the 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 class I locus. The second system involves similar manipulations of miniature swine bone marrow, with the goal of inducing tolerance to class II antigens, since these antigens have been shown to be of overwhelming importance in determining the fate of vascularized allografts in this model. In vitro data in a bone marrow culture system indicate that an appropriate vector for this purpose has been produced.