Allogeneic Chimerism Induced by Low Dose of Peripheral Blood Stem Cells Combined with Splenocytes in Sublethally Irradiated Mice
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Background: We previously demonstrated that a high level of chimerism was induced by low dose of bone marrow cells (BMCs) combined with splenocytes (SPLCs), while the same dose of BMCs alone was insufficient for tolerance induction. In the present study, we investigated whether stable mixed chimerism and donor specific tolerance could be established in sublethally irradiated mice following intravenous injection of various dosages of fully allogeneic peripheral blood stem cells (PBSCs). In addition, validity of combination of donor splenocytes in the peripheral blood stem cell transplantation (PBSCT) as well as in bone marrow transplantation for tolerance induction were examined. Methods: Sublethally irradiated C57BL/6 recipient mice were injected 10×10^6 PBSCs mixed with various numbers of granulocyte-colony-stimulating factor (G-CSF)-mobilized SPLCs harvested from BALB/c donor mice. Three months later, the degree of chimerism in peripheral blood lymphocytes and in SPLCs was examined by FACS analysis. Mixed lymphocyte responses (MLR) and skin grafting were performed to confirm donor-specific tolerance. Results: Recipients receiving 10×10^6 PBSCs mixed with 30×10^6 G-CSF-mobilized SPLCs showed a higher level of chimerism. High percentage chimeric mice all showed donor specific tolerance in vitro, MLR and in vivo, and skin grafting. Conclusions: PBSCT mixed with SPLCs was proven to be useful for induction of donor-specific tolerance. Admixture of SPLCs reduces the amount of PBSCs needed for induction of tolerance.
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