Abstract:
:Adenovirus vectors transduce liver hepatocytes with extreme efficiency; however, transgene expression is eliminated within 2 weeks. Extinction of transgene expression has been attributed to infiltrating cytotoxic T lymphocytes (CTLs) in the liver in a process that resembles a number of human diseases, including viral and autoimmune hepatitis. In this study we investigated the role of Fas-Fas ligand interactions in killing of vector-transduced hepatocytes in vitro and in vivo. Intrahepatic lymphocytes (IHLs) isolated from livers of mice administered adenovirus vector demonstrated cytolytic activity against vector-infected primary hepatocytes. The in vitro CTL activity of the IHLs involving both CD4+ and CD8+ T cells was MHC class I restricted and could be blocked by soluble Fas-IgG. Adoptive transfer of IHLs from immune-competent mice immunized with Ad-lacZ into Ragl-deficient mice previously infused with Ad-lacZ resulted in rapid elimination of beta-galactosidase-transduced hepatocytes. Transfer of these cells into Fas-deficient mice (B6-lpr) failed to eliminate lacZ expression; likewise IHLs from immunized FasL-deficient mice (B6-gld) failed to eliminate lacZ expression in Rag1-deficient mice. Finally, in vivo administration of soluble Fas-IgG abrogated the ability of Ad-lacZ-primed IHLs to eliminate transgene expression. These studies establish an essential role for Fas-Fas ligand interactions in the mechanism of elimination of adenoviral vector-mediated transgene expression in the liver.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Chirmule N,Moscioni AD,Qian Y,Qian R,Chen Y,Wilson JMdoi
10.1089/10430349950019048keywords:
subject
Has Abstractpub_date
1999-01-20 00:00:00pages
259-69issue
2eissn
1043-0342issn
1557-7422journal_volume
10pub_type
杂志文章abstract::The objective of this phase II investigation is to assess the safety and efficacy of a plasmid mediated approach to induce angiogenesis/arteriogenesis with the angiomatrix protein Del-1 (developmentally regulated endothelial locus 1), in subjects with intermittent claudication (IC) secondary to peripheral arterial dis...
journal_title:Human gene therapy
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
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journal_title:Human gene therapy
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journal_title:Human gene therapy
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journal_title:Human gene therapy
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journal_title:Human gene therapy
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journal_title:Human gene therapy
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1998.9.6-771
更新日期:1998-04-10 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2005.16.1116
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journal_title:Human gene therapy
pub_type: 杂志文章
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journal_title:Human gene therapy
pub_type: 杂志文章
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更新日期:1996-08-20 00:00:00
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pub_type: 杂志文章
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journal_title:Human gene therapy
pub_type: 杂志文章
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journal_title:Human gene therapy
pub_type: 杂志文章
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