Apoptotic donor leukocytes inhibit tolerance and limit mixed chimerism induced by CD40-CD154 blockade in allogeneic bone marrow transplantation

Abstract

Background: “Mini” transplants using non-myeloablative conditioning can avoid early post-transplant toxicity associated with myeloablative conditioning prior to allogeneic hematopoietic progenitor cell transplantation (HPCT), but graft-versus-host-disease (GvHD) and graft rejection remain clinical problems. We previously found that low-dose busulfan conditioning and costimulatory blockade using anti-CD154 monoclonal antibody (mAb) were sufficient to establish stable mixed chimerism without GvHD when transplanting moderate doses of T cell depleted bone marrow (TCD-BM) from MHC fully mismatched donors (Adams et al, J Immunol 167:1103, 2001).