HEMATOPOIETIC STEM-CELLS CAN INDUCE SPECIFIC SKIN-GRAFT ACCEPTANCE ACROSS FULL MHC BARRIERS

Previously, we and others have demonstrated in several animal models t hat the establishment of stable haematopoietic chimerism through allog eneic bone marrow transfusion provides an effective means for the deve lopment of specific transplantation tolerance. However, a major limita tion to the clinical application of allogeneic bone marrow transfusion in immunosuppressed recipients for induction of tolerance to solid gr afts, is the risk of graft-versus-host disease (GVHD), Therefore, it i s important to identify the cell population needed for the induction o f mixed chimerism and tolerance, Haematopoietic stem cells have the ca pacity of self-renewal and multilineage differentiation, and have been shown to reduce the risk of GVHD, We studied transfusion of two rich sources of stem cells, namely allogeneic fetal liver cells and a subse t of purified bone marrow-derived progenitor cells (c-kit(+)) into ant i-T cell monoclonal antibody-treated, low-dose irradiated recipient mi ce, Our data revealed that stable multilineage mixed chimerism and per manent donor-specific tolerance for skin, even when transplanted direc tly following conditioning, can be successfully achieved in this way, with no signs of GVHD.