Compositions and methods for inducing chimerism in a subject

摘要

Prevention of autoimmune disease and induction of transplantation tolerance in a recipient can be achieved by induction of mixed chimerism via bone marrow transplantation (BMT), but this procedure requires total body irradiation (TBI)-conditioning of the recipient. The toxicity of radiation and potential for graft versus host disease (GVHD) prevents its clinical application. Donor CD8⁺ T cells play a critical role in facilitation of engraftment, but also contribute to induction of GVHD in TBI-conditioned recipients. It is disclosed herein that high doses of donor CD8⁺ T cells in combination with donor bone marrow (BM) cells induces mixed chimerism without GVHD in recipients conditioned with anti-CD3 mAb. These chimeric recipients display donor specific tolerance and reversal of insulitis. These results establish that donor CD8⁺ T cell-mediated facilitation of engraftment can be separated from GVHD in non-irradiated recipients. This regimen has application in the treatment of autoimmune disorders and the induction of transplantation tolerance.