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Blood, 1 February 2004, Vol. 103, No. 3, pp. 811-819. Prepublished online as a Blood First Edition Paper on October 9, 2003; DOI 10.1182/blood-2003-02-0524. This Article Full Text (PDF) All Versions of this Article: 2003-02-0524v1 103/3/811    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Larregina, A. T Articles by Falo, L. D Search for Related Content PubMed PubMed Citation Articles by Larregina, A. T Articles by Falo, L. D Social Bookmarking                   What's this? Submitted February 19, 2003 Accepted September 26, 2003 Highly efficient expression of transgenic proteins by naked DNA transfected dendritic cells through terminal differentiation Adriana T Larregina*, Adrian E Morelli, Olga Tkacheva, Geza Erdos, Cara Donahue, Simon C Watkins, Angus W Thomson, and Louis D Falo Department of Dermatology, University of Pittsburgh, Pittsburgh, PA, USA Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA Department of Phisiology, University of Pittsburgh, Pittsburgh, PA, USA Center for Genomic Sciences, Allegheny General Hospital, Pittsburgh, PA, USA * Corresponding author; email: adrianal{at}pitt.edu. Dendritic cells (DCs) play a key role in the induction and control of immunity. Genetic engineering of DCs is a promising approach for the development of a broad range of immunomodulatory strategies, for purposes ranging from genetic immunization to tolerance induction. The development of DC-based immunotherapies is limited by inability to efficiently transfect DCs using naked DNA. Here we demonstrate that following plasmid DNA delivery, transgene expression controlled by human immediately early cytomegalovirus promoter (hIE-CMVp) is higher in mature DCs than in immature DCs, and it is further increased after terminal differentiation of DCs by agonist anti-CD40 monoclonal antibody (mAb), or following DC interaction with CD4pos T cells. CD40-signaling of DCs resulted in nuclear translocation of the transcription factors nuclear factor- Beta (NF-B), activator of protein-1 (AP-1) and cAMP responsive element (CRE), necessary for activation of hIE-CMVp. Transgene expression by DCs diminished after inhibition of these transcription factors or blockade of the adhesion molecules involved in DC-T cell synapse. Importantly CD40 signaling of DC results in highly efficient expression and presentation of transgenic antigens (Ag) and induction of "in vivo" cytotoxic T cell (CTLs) response specific for transgenic Ag peptides, demonstrating the functional potential of genetically engineering DCs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. M. Janelsins, A. R. Mathers, O. A. Tkacheva, G. Erdos, W. J. Shufesky, A. E. Morelli, and A. T. Larregina Proinflammatory tachykinins that signal through the neurokinin 1 receptor promote survival of dendritic cells and potent cellular immunity Blood, March 26, 2009; 113(13): 3017 - 3026. [Abstract] [Full Text] [PDF] N. M. Melhem, S. M. Gleason, X. D. Liu, and S. M. Barratt-Boyes High-Level Antigen Expression and Sustained Antigen Presentation in Dendritic Cells Nucleofected with Wild-Type Viral mRNA but Not DNA Clin. 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Immunol., October 15, 2006; 177(8): 5278 - 5289. [Abstract] [Full Text] [PDF] M. J. Perone, A. T. Larregina, W. J. Shufesky, G. D. Papworth, M. L. G. Sullivan, A. F. Zahorchak, D. B. Stolz, L. G. Baum, S. C. Watkins, A. W. Thomson, et al. Transgenic galectin-1 induces maturation of dendritic cells that elicit contrasting responses in naive and activated T cells. J. Immunol., June 15, 2006; 176(12): 7207 - 7220. [Abstract] [Full Text] [PDF] Y. He, J. Zhang, Z. Mi, P. Robbins, and L. D. Falo Jr Immunization with Lentiviral Vector-Transduced Dendritic Cells Induces Strong and Long-Lasting T Cell Responses and Therapeutic Immunity J. Immunol., March 15, 2005; 174(6): 3808 - 3817. [Abstract] [Full Text] [PDF] D. W. O'Neill, S. Adams, and N. Bhardwaj Manipulating dendritic cell biology for the active immunotherapy of cancer Blood, October 15, 2004; 104(8): 2235 - 2246. [Abstract] [Full Text] [PDF]

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