Gene Transfer of Antisense B7.1 Attenuates Acute Rejection Against Liver Allografts in Rats
Gene Transfer of Antisense B7.1 Attenuates Acute Rejection Against Liver Allografts in Rats
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反义 B7.1 的基因转移可减轻大鼠同种异体肝脏移植物的急性排斥反应
DOI：
10.3109/08941930903469359
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发表时间：
2010
影响因子：
1.9
通讯作者：
Xueying Sun
中科院分区：
文献类型：
--
作者：
Y. Mi;Rui Li;Kesen Xu;Hongchi Jiang;Xueying Sun
摘要目的：阻断CD 80-CD 28共刺激通路可诱导T细胞对同种异体抗原的无反应性，并保护同种异体移植物免受免疫排斥。本研究旨在探讨反义B7.1基因转染下调供肝中B7.1（CD 80）的表达是否能减轻大鼠肝移植急性免疫排斥反应。研究方法：将反义B7.1表达载体经门静脉灌注于60只Dark Agglutinus大鼠的肝移植物中，然后移植到刘易斯大鼠体内。空载体pcDNA 3作为对照，灌注到另一组60只Dark Aggregated大鼠的肝脏中。行原位肝移植术。在预定的时间点随机处死大鼠以收集同种异体肝移植物，或监测以记录存活率。取肝组织行组织学检查，计算Banff排斥指数，免疫印迹法、免疫组化法检测B7.1表达，CD 4+、CD 8+细胞计数。结果如下：反义基因转染可显著下调供肝中B7.1的表达，减轻供肝急性免疫排斥反应，延长大鼠存活时间，减少肝脏中CD 4+和CD 8+细胞浸润。结论：通过反义基因治疗阻断肝脏B7.1的表达可能是减轻肝移植急性排斥反应的一种潜在策略。
ABSTRACT Objective: Blockade of CD80-CD28 costimulatory pathway induces unresponsiveness of T cells to alloantigens and protects allografts against immune rejection. The aim of this study was to investigate whether downregulating the expression of B7.1 (CD80) in the donor livers by antisense B7.1 gene transfer could attenuate the acute immune rejection against liver allografts in rats. Methods: The liver grafts from 60 Dark Agouti rats were intraportally perfused with antisense B7.1 expression vector, before they were transplanted into Lewis rats. Empty vector pcDNA3 served as control to be perfused into livers of another group of 60 Dark Agouti rats. The orthotopic liver transplantation was performed. The rats were randomly sacrificed at scheduled time points to collect liver allografts, or monitored to record the survival rate. The livers were histologically examined to calculate Banff rejection activity index, or subjected to Western blot analysis or immunohistochemistry for examining the expression of B7.1, or counting CD4+ and CD8+ cells. Results: Antisense gene transfer resulted in markedly downregulation of B7.1 in the donor livers, attenuated acute immune rejection against liver allografts, prolonged the survival time of rats, and decreased the number of infiltrating CD4+ and CD8+ cells in livers. Conclusions: Blocking expression of B7.1 in liver by antisense gene therapy may represent a potential strategy to attenuate acute rejection against liver allografts.