非清髓造血干细胞移植后致敏供者淋巴细胞输注对嵌合状态及GVHD影响的实验研究_医学论文.docVIP

非清髓造血干细胞移植后致敏供者淋巴细胞输注对嵌合状态及GVHD影响的实验研究_医学论文 非清髓造血干细胞移植后致敏供者淋巴细胞输注对嵌合状态及GVHD影响的实验研究_医学论文 作者：陈宝安，张琰，丁家华，毕延智，赵刚，高冲，孙耘玉，孙雪梅，王骏，陈宁娜，程坚【摘要】 本研究目的是探讨经受者皮肤致敏后的异基因供者淋巴细胞输注（DLI）是否能在促进形成完全供者嵌合（CC）的同时减轻移植物抗宿主病（GVHD）。以C57BL/6小鼠（H-2b，B6）为受者，于第0天接受60Co γ线全身照射（TBI），总剂量为5.5 Gy，照射当天移植经粒细胞集落刺激因子（G-CSF）动员后的BALB/c小鼠（H-2d，BA）外周血干细胞（2×107个），移植后第2天腹腔注射环磷酰胺200 mg/kg，并分别于移植后第28天输注致敏/未致敏的供者淋巴细胞2×106。结果显示，致敏后DLI的受鼠（黑色）无1例出现GVHD，60天时转变为完全供者嵌合，表型明显呈现为供鼠（白色）特征，CD4+/CD8+T淋巴细胞比值在DLI后早期下降，半月后有所升高，但仍低于正常水平；未致敏的DLI受鼠出现不同程度的GVHD，嵌合率稍有上升，仍表现为混合嵌合体（MC），CD4+/CD8+比值在DLI后早期升高，后期降至正常水平。结论：经受者皮肤致敏后的DLI在诱导CC的同时降低GVHD发病率，CD4+/CD8+比值与GVHD发病率间具有良好的相关性。 【关键词】 非清髓性异基因造血干细胞移植 　　Effects of Sensitized Donor Lymphocyte Infusion on the Chimerism and Graft-versus-Host Disease after Nonmyeloablative Allogeneic Stem Cell Transplantation 　Abstract To explore whether the complete donor chimerism could be achieved and graft-versus-host disease could be alleviated by donor lymphocyte infusion which was sensitized by the skin of the recipient，female C57BL/6 mice (H-2b，B6) as recipients received total body irradiation (TBI) of 5.5 Gy (60Co γ-ray) on day 0 followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). The allo-grafts consisted of 2×107 peripheral hematopoietic stem cells from mobilized male BALB/c (H-2d) donor mice with the granulocyte colony-stimulating factor (G-CSF). Day 2 after allo-HSCT，the recipient mice were given 200 mg/kg cyclophosphamide intraperitoneally. Afterwards these recipient mice were infused 2×106 sensitized or unsensitized-donor lymphocytes at the 28 days after transplantation. The results showed that the mice receiving sensitized-donor lymphocyte infusion did not suffer from GVHD and the phenotypic character of the recipient mice (black color) converted to that of the donor mice (white color)，and to become full-donor chimerism. It was found that the ratio 0f CD4+/CD8+ T lymphocytes of them decreased at the earlier period and increased after half month，but which were also lower t