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学科主题: 基础医学
题名:
Adenovirus-mediated CTLA4-FasL gene transfer prevents autoimmune diabetes in mice induced by multiple low doses of streptozotocin
作者: Jin, YZ; Wang, GM; Li, AL; Hao, J; Gao, X; Xie, SS
关键词: insulin-dependent diabetes mellitus ; adenoviral vectors ; streptozotocin ; gene therapy ; apoptosis
刊名: CHINESE SCIENCE BULLETIN
发表日期: 2004-03-01
DOI: 10.1360/03wc0532
卷: 49, 期:5, 页:476-481
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: FAS LIGAND ; EXPRESSION ; MELLITUS ; CELLS
英文摘要:

Type 1 diabetes is the result of a selective destruction of insulin-producing P cells in pancreatic islets by autoreactive T cells. Depletion of autoreactive T cell through apoptosis may be a potential strategy for the prevention of autoimmune diabetes. Simultaneous stimulation of Fas-mediated pathway and blockade of costimulation by a CTLA4-FasL fusion protein has been reported to lead to substantial inhibition of mixed lymphocyte reaction and enhanced in vitro apoptosis of peripheral lymphocytes. To test the feasibility of CTLA4-FasL- based gene therapy to prevent autoimmune diabetes, we developed recombinant adenovirus containing human C7LA4-FasL gene (Ad-CTLA4-FasL). A single injection of 2X10(8) plaque forming units (PFU) of AdCTLA4-FasL via tail vein dramatically reduced the incidence of autoimmune diabetes in mice induced by multiple low doses of streptozotocin. AdCTLA4-FasL administration maintained islet insulin content, significantly increased apoptosis of pancreatic lymphocytes, quantitatively reduced IFN-gamma and Vbeta8.2 TCR chain mRNA expression in pancreatic lymphocytes. These results indicate the therapeutic potential of simultaneous stimulation of Fas-mediated pathway and blockade of costimulation by adenovirus-mediated CTLA4-FasL gene transfer in the prevention of autoimmune diabetes.

语种: 英语
WOS记录号: WOS:000221118900012
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58585
Appears in Collections:基础医学院_免疫学系_期刊论文

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作者单位: Peking Univ, Ctr Hlth Sci, Dept Immunol, Beijing 100083, Peoples R China

Recommended Citation:
Jin, YZ,Wang, GM,Li, AL,et al. Adenovirus-mediated CTLA4-FasL gene transfer prevents autoimmune diabetes in mice induced by multiple low doses of streptozotocin[J]. CHINESE SCIENCE BULLETIN,2004,49(5):476-481.
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