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Effects of regulatory dendritic cells on graft-versus-host disease and graft-versus-leukemia in mice after allogeneic bone marrow transplantation
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摘要
Objective:We investigated the effect of regulatory dendritic cells(DCreg) on acute graft-versus-host disease(GVHD) and graft-versus-leukemia(GVL) in leukemia mouse models after allogeneic bone marrow transplantation(allo-BMT).Method:A SHI-1 leukemia allo-BMT model of C57BL/6 to BABL/c mice was established.DCreg with donor bone marrow cells and splenocytes were subsequently transplanted into myeloablatively irradiated recipients.The animals were divided into the TBI(total body irradiation),leukemia,allo-BMT,and immature DC(im DC),and DCreg groups.Result:Recipient survival time in the DCreg and im DC groups was significantly prolonged compared with that in alloBMT group(P < 0.05).Moreover,mild histological changes of GVHD or leukemia were observed in recipients in DCreg group,and clinical GVHD scores in this group were significantly decreased compared with those in transplantation group and im DC group.Furthermore,the allogeneic chimerism rate was still 95-100% in DCreg group,suggesting complete donor type implantation.Serum interferon-γ level decreased in the im DC and DCreg groups compared with that in allo-BMT group and even more significantly reduced in DCreg(P < 0.01).Additionally,Serum interleukin-10 level gradually increased in the im DC and DCreg groups(P< 0.01) whereas decreased in the allo-BMT group.Conclusion:DCreg cell infusion successfully improved incidence and severity of GVHD in allo-BMT mouse models,while could also preserve the effect of GVL
Objective:We investigated the effect of regulatory dendritic cells(DCreg) on acute graft-versus-host disease(GVHD) and graft-versus-leukemia(GVL) in leukemia mouse models after allogeneic bone marrow transplantation(allo-BMT).Method:A SHI-1 leukemia allo-BMT model of C57BL/6 to BABL/c mice was established.DCreg with donor bone marrow cells and splenocytes were subsequently transplanted into myeloablatively irradiated recipients.The animals were divided into the TBI(total body irradiation),leukemia,allo-BMT,and immature DC(im DC),and DCreg groups.Result:Recipient survival time in the DCreg and im DC groups was significantly prolonged compared with that in alloBMT group(P < 0.05).Moreover,mild histological changes of GVHD or leukemia were observed in recipients in DCreg group,and clinical GVHD scores in this group were significantly decreased compared with those in transplantation group and im DC group.Furthermore,the allogeneic chimerism rate was still 95-100% in DCreg group,suggesting complete donor type implantation.Serum interferon-γ level decreased in the im DC and DCreg groups compared with that in allo-BMT group and even more significantly reduced in DCreg(P < 0.01).Additionally,Serum interleukin-10 level gradually increased in the im DC and DCreg groups(P< 0.01) whereas decreased in the allo-BMT group.Conclusion:DCreg cell infusion successfully improved incidence and severity of GVHD in allo-BMT mouse models,while could also preserve the effect of GVL
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