Long-Term Tolerance to Kidney Allografts After Induced Rejection of Donor Hematopoietic Chimerism in a Preclinical Canine Model

Background: Allogeneic hematopoietic cell transplantation provides a reliable method for inducing tolerance toward solid organ grafts. However, this procedure can result in graft-versus-host disease, thereby limiting its application. Here, we test the hypothesis that mixed chimerism can be intentionally reverted to host hematopoiesis without rejection of a kidney graft.
Methods: Recipient dogs were given 2-Gy total-body irradiation (TBI) before and a short course of immunosuppression after marrow infusion from dog leukocyte antigen–identical littermates. All dogs achieved stable mixed chimerism. After a mean of 20 weeks, one cohort of dogs received kidney transplants from their respective marrow donors. Subsequently, recipients were reconditioned with 2-Gy TBI and given autologous granulocyte colony-stimulating factor–mobilized leukocytes (recipient leukocyte infusion [RLI]) that had been collected before marrow transplantation.
Results: Dogs receiving a second TBI and RLI without a kidney transplant rejected their donor hematopoietic graft within 3 weeks. Dogs that received kidney grafts, followed by a second TBI and RLI, rejected their marrow graft without rejecting their transplanted kidneys for periods greater than 1 year.
Conclusion: Mixed chimerism may be clinically reverted to 100% recipient without rejection of a kidney allograft. This finding may have application toward minimizing the risk of graft-versus-host disease in solid organ transplantation patients given hematopoietic cell transplantation from human leukocyte antigen–identical donors (read more). Print this post