| Shutdown of immunological priming and presentation after in vivo administration of adenovirus. | |
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MedLine Citation:
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PMID: 22089496 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Adenoviral (Adv) vectors are widely used in both experimental and clinical trials for vaccination and gene therapy. Recombinant Adv can evoke potent innate immune responses and adaptive immune responses to encoded antigens. However, how Adv infection affects the response to subsequently encountered antigens is poorly understood. We show that intravenously administered replication defective (E1 and E3 deleted) Adv educes functional changes in dendritic cells (DC) resulting in impaired priming of cytotoxic T lymphocytes (CTL) more than 7 days after Adv treatment. Generalized DC activation was indicated by transient upregulation of CD86 and reduced endocytosis of fluorescent beads. It is known that CD8+ DC are predominantly responsible for uptake and presentation (cross-presentation) of exogenous antigens to CD8+ CTL. Hence, impaired endocytosis in CD8+, but not CD8-, DC at 7 days after Adv administration provided an explanation for the impaired CTL response to antigen at this time. Shutdown of cross-presentation was confirmed using cytochrome c (cytc), an agent that selectively depletes cross-presenting DC. Adv-infection rendered CD8+ DC resistant to depletion by cytc. As the cross-presentation pathway underlies CD8 T-cell responses to many cancers and to vaccines or viruses that do not directly infect DC, systemic Adv administration may impair these responses.Gene Therapy advance online publication, 17 November 2011; doi:10.1038/gt.2011.187. |
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Authors:
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R M Sutherland; S L Londrigan; J L Brady; H Azher; E M Carrington; Y Zhan; J Vega-Ramos; J A Villadangos; A M Lew |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-17 |
Journal Detail:
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Title: Gene therapy Volume: - ISSN: 1476-5462 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-17 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9421525 Medline TA: Gene Ther Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1] The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia [2] Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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