NON-LETHAL CONDITIONING METHODS FOR CONDITIONING A RECIPIENT FOR BONE MARROW TRANSPLANTATION

摘要

Mixed chimerism induces donor-specific transplantation tolerance to organ allografts. In this invention, recipient B10 (h2b) mice were pretreated in vivo with anti-aβ-TCR and anit-CD8 mABs 3 days before total body irradiation (TBI) and transplanted with 15 X 106 allogenic (B10.BR; H2k) marrow cells. Engraftment occurred in 20%, 75% and 94% of animals conditioned with 100, 200 or 300 cGy TBI one month post bone marrow transplant (BMT), respectively. Animals without donor T cells lost their chimerism gradually within 6 months and rejected both donor and third-party skin grafts. In animals with donor T cell production, chimerism remained stable for ≥ 6 months and donor skin grafts were accepted. In the animals without donor T cell production, none of the expected stages of T cell development were present in the thymus, while in those with donor T cell production they were. Moreover, clonal deletion of Vβ 5.1/2+ and Vβ 11+ CD8 and CD4 T cells occurred only in chimeras with donor T cell production. These results show for the first time that donor T cell production plays a critical role in the maintenance of durable chimerism and induction of trnaplantation tolerance and is directly correlated with deletion of potentially autoreactive cells.