FasL基因修饰骨髓树突状细胞诱导小鼠心脏移植免疫耐受的实验研究
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An experimental study on inducement of mouse cardiac transplantation tolerance by dendritic cells genetically engineered to express Fas Ligand
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    摘要:

    目的:探讨 FasL基因转染骨髓来源树突状细胞术前免疫受者在诱导同种小鼠心脏移植耐受中的作用。方法: 采用腺病毒载体将FasL基因转染骨髓来源树突状细胞,将基因修饰的DC经尾静脉输入预处理BALB/c受者小鼠,观察移植心脏的存活时间,通过混合淋巴细胞反应(MLR)检测抗原特异性T淋巴细胞的低反应性。结果:AdFasL-DC组移植心脏存活期为21.5 ± 2.5天,Day-7-DC和LacZ-DC处理组移植心脏存活时间为9.5 ± 1.5天和10.0 ± 2.0天,FasL-DC术前免疫受者可使同种移植物存活时间明显延长(P < 0.05);MLR结果显示 FasL-DC处理组与对照组相比显著地抑制了T淋巴细胞的增埴(P < 0.05)。结论:FasL基因转染DC能够诱导同种反应性T淋巴细胞凋亡,术前免疫受者能使同种移植物存活时间得到延长。

    Abstract:

    Objective:To explore the effect and mechanisms of immune tolerance induced by injecting dendritic cells transfected with Fas ligand gene in allograft recipients. Methods:DCs were prepared from mouse bone marrow and genetically modified by Fas ligand. FasL-DC and LacZ-DC pooled from C57BL/6 donors were iv injected into BALB/c befor transplantation. The propliferative ability of T lymphocytes with the mixed lympiocyte reaction(MLR) was performed to further explore tolerance mechanisms. Results:The Fas ligand gene could be transfected into BMDC and expressed efficiently. The pretreatment of AdFasL modified DC greatly prolonged the survival of cardiac grafts in the recipients,extending survival from 10.0 ± 2.0 days(in LacZ-DC group) and 9.5 ± 1.5 days(in Day-7-DC group) to 21.5 ± 2.5 days. The result of MLR showed that allogeneic T lympiocyte cell proliferation was decreased significantly. Conclusion:The DC transfected with Fas ligand could induce apoptosis of the allogeneic reative T lymphocytes,and pretreatment of AdFasL modified DC could prolonged the survival of cardiac grafts in the recipients.

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张传永,钱晓峰,王 科,王 平,王学浩. FasL基因修饰骨髓树突状细胞诱导小鼠心脏移植免疫耐受的实验研究[J].南京医科大学学报(自然科学版),2007,(11):1278-1280

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  • 收稿日期:2007-05-19
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