Allogeneic inducible regulatory T cells allow the generation of mixed chimerism via nonmyeloablative conditioning in mice models (126.5)

Abstract

Abstract It has been demonstrated that the generation of mixed chimerism induces stable tolerance in allogeneic transplant organs. Current protocols require myeloablative or nonmyeloablative conditioning, both involving physical, pharmacological and/or cellular conditioning in order to produce general immunosuppression. Here, we have successfully developed a protocol that produces mixed chimerism using inducible allogeneic regulatory T cells (iTreg), low dose irradiation (3 Gy) and the FDA approved immunosuppressive drugs Rapamycin and Abatacept. Under experimental conditions, allogeneic iTreg treated mice produced mixed chimerism whereas, control mice lacking iTreg, rejected allogeneic bone marrow transplantation. Additionally, chimeric mice are able to accept secondary allogeneic skin transplants. Therefore we propose that generation of mixed chimerism is an improved specific therapy designed for stable alloinjert tolerance induction.