An MHC-defined primate model reveals significant rejection of bone marrow after mixed chimerism induction despite full MHC matching.

ABSTRACT: In murine models, mixed hematopoietic chimerism induction leads to robust immune tolerance. However, translation to primates and to patients has been difficult. In this study, we used a novel MHC-defined rhesus macaque model to examine the impact of MHC matching on the stability of costimulation blockade-/sirolimus-mediated chimerism, and to probe possible mechanisms of bone marrow rejection after nonmyeloablative transplant. Using busulfan-based pretransplant preparation and maintenance immunosuppression with sirolimus, as well as CD28 and CD154 blockade, all recipients demonstrated donor engraftment after transplant. However, the mixed chimerism that resulted was compartmentalized, with recipients demonstrating significantly higher whole blood chimerism compared to T cell chimerism. Thus

SUBMITTER: Larsen CP 

PROVIDER: S-EPMC2980834 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature