Induction of chimerism in rhesus macaques through stem cell transplant and costimulation blockade-based immunosuppression.

摘要: A strategy for producing high-level hematopoietic chimerism after non-myeloablative conditioning has been established in the rhesus macaque. This relies on stem cell transplantation induction with a dose of busulfan and blockade IL2-receptor setting mTOR inhibition sirolimus combined CD28/CD154 costimulation blockade. Hematopoietic cells derived from bone marrow leukopheresis products both were found to be successful inducing chimerism. Mean peripheral blood peak donor was 81% median duration 145 days. Additional immune modulation strategies, such as pre-transplant CD8 depletion, donor-specific transfusion, recipient thymectomy or peritransplant deoxyspergualin treatment did not improve level durability Recipient immunologic assessment suggested that occurred amidst down-regulation alloreactive T cells, reappearance vigorous T-mediated alloreactivity accompanied rejection transplants. Furthermore, viral reactivation constituted significant transplant-related toxicity may have negatively impacted ability achieve indefinite survival transplanted cells. Nevertheless, this chimerism-induction regimen induced amongst longest-lived reported date non-human primates thus represents platform upon which evaluate emerging tolerance-induction strategies.