Severe Impairment of Dendritic Cell Allostimulatory Activity by Sendai Virus Vectors Is Overcome by Matrix Protein Gene Deletion
| Autor: | Ulrich M. Lauert, Sascha Bossow, Irina Smirnov, Wolfgang J. Neubert, Peter Brossart, Guy Ungerechts, Michael Bitzer, Christian Bernloehr, Sorin Armeanu, Silke Appel, Lothar Kanz |
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| Rok vydání: | 2005 |
| Předmět: | |
| Zdroj: | Blood. 106:5535-5535 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Delivery of antigens to dendritic cells (DCs) plays a pivotal role in the induction of efficient immune responses ranging from immunity to tolerance. The observation that certain viral pathogens are able to infect DCs has led to a concept where applications of recombinant viruses are employed for antigen delivery with the potential benefit of inducing potent antigen specific T-cell responses directed against multiple epitopes. As a prerequisite for such an application, the infection of DCs by recombinant viruses should not interfere with their stimulatory capacity. In this context we could show, that an emerging neagtive-strand RNA viral vector system based on Sendai virus (SeV) is able to efficiently infect monocyte derived human DCs (moDCs). However, after infection with SeV wildtype the responses of DCs to bacterial lipopolysaccharide (LPS) as a powerful mediator of DC maturation characterized by upregulation of CD83, MHC and costimulatory molecules, enhanced secretion of cytokines and the T cell stimulatory capacity were severly impaired. This was not due to a higher production of IL-10 or inhibition of the nuclear localized expression of Rel-B and c-rel, members of the NF-kB transcription factor family, but was rather the result of an increased apoptosis induction of DC. Interestingly, using various recombinant SeV vectors being devoid of single viral genes we were able to identify the SeV matrix (M) protein as a key component in moDC functional impairment after viral infection. Consequently, usage of M-deficient SeV vectors preserved the allostimulatory activity in infected moDCs despite an efficient expression of all other virally encoded genes, thereby identifying M-deficient vectors as a highly potent tool for the genetic manipulation of DCs. |
| Databáze: | OpenAIRE |
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