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Blood, 15 May 2005, Vol. 105, No. 10, pp. 3824-3832. Prepublished online as a Blood First Edition Paper on January 25, 2005; DOI 10.1182/blood-2004-10-3880. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: 2004-10-3880v1 105/10/3824    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 Tan, P. H Articles by George, A. J Search for Related Content PubMed PubMed Citation Articles by Tan, P. H Articles by George, A. J Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 7, 2004 Accepted January 4, 2005 Modulation of human dendritic cell function following transduction with viral vectors; implications for gene therapy Peng H Tan, Sven C Beutelspacher, Shao-An Xue, Yao-He Wang, Peter Mitchell, James C McAlister, D F Larkin, Myra O McClure, Hans J Stauss, Mary A Ritter, Giovanna Lombardi, and Andrew J George* Department of Immunology, Imperial College, London, United Kingdom Department of Immunology, Imperial College, London, United Kingdom; Jefferiss Research Trust Laboratories, Write-Fleming Institute, Division of Medicine, Faculty of Medicine, Imperial College London, St Mary's Hospital, London, United Kingdom Cancer Research UK Molecular Oncology Unit, Division of Medicine, Faculty of Medicine, Imperial College, London, United Kingdom Moorfields Eye Hospital, London, United Kingdom; Department of Molecular Genetics, Institute of Ophthalmology, University College, London, United Kingdom Department of Immunology, Imperial College, London, United Kingdom; Moorfields Eye Hospital, London, United Kingdom; Department of Molecular Genetics, Institute of Ophthalmology, University College, London, United Kingdom Jefferiss Research Trust Laboratories, Write-Fleming Institute, Division of Medicine, Faculty of Medicine, Imperial College London, St Mary's Hospital, London, United Kingdom * Corresponding author; email: a.george{at}imperial.ac.uk. Genetic modification of dendritic cell (DC) function is an attractive approach to treat disease; either using mature DCs (mDCs) to immunize patients, or immature DCs (iDCs) to induce tolerance. Viral vectors are efficient at transducing DCs, and we have investigated the effect of transduction with a variety of viral vectors on the phenotype and function of DCs. Adenovirus (Ad), human immunodeficiency virus (HIV), equine anaemia virus (EIAV) and Moloney murine leukemia virus (MMLV) all upregulate co-stimulatory molecules and MHC class II expression on DC, as well as, in the case of Ad and lentiviral vectors, inducing production of Th1 and proinflammatory cytokines. Following transduction there is activation of dsRNA-triggered pathways resulting in IFN/ production. In addition, the function of virally-infected DCs is altered; iDCs have an increased, and mDCs a decreased, ability to stimulate a mixed lymphocyte reaction (MLR). Viral transduction of mDC results in upregulation of the indoleamine 2,3-dioxygenase (IDO) enzyme, which downregulates T cell responsiveness. Inhibition of IDO restores the ability of mDC to stimulate a MLR, indicating that IDO is responsible for the modulation of mDC function. These data have important implications for the use of viral vectors in the transduction of DC. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: A cautionary tale David H. Munn Blood 2005 105: 3761-3762. [Full Text] [PDF] This article has been cited by other articles: H. M. Rowe, L. Lopes, N. Brown, S. Efklidou, T. Smallie, S. Karrar, P. M. Kaye, and M. K. Collins Expression of vFLIP in a Lentiviral Vaccine Vector Activates NF-{kappa}B, Matures Dendritic Cells, and Increases CD8+ T-Cell Responses J. Virol., February 15, 2009; 83(4): 1555 - 1562. [Abstract] [Full Text] [PDF] M. Perreau, F. Mennechet, N. Serratrice, J. N. Glasgow, D. T. 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Diebold, S. Gschmeissner, Y. Takeuchi, Y. Ikeda, M. K. Collins, and C. Reis e Sousa Tubulovesicular Structures within Vesicular Stomatitis Virus G Protein-Pseudotyped Lentiviral Vector Preparations Carry DNA and Stimulate Antiviral Responses via Toll-Like Receptor 9 J. Virol., January 15, 2007; 81(2): 539 - 547. [Abstract] [Full Text] [PDF] H. Akbulut, Y. Tang, K. G. Akbulut, J. Maynard, L. Zhang, and A. Deisseroth Antitumor immune response induced by i.t. injection of vector-activated dendritic cells and chemotherapy suppresses metastatic breast cancer. Mol. Cancer Ther., August 1, 2006; 5(8): 1975 - 1985. [Abstract] [Full Text] [PDF] H. Liu, L. Liu, B. S. Fletcher, and G. A. Visner Novel Action of Indoleamine 2,3-Dioxygenase Attenuating Acute Lung Allograft Injury Am. J. Respir. Crit. Care Med., March 1, 2006; 173(5): 566 - 572. [Abstract] [Full Text] [PDF] P. H. Tan, S.-A. Xue, M. Manunta, S. C. Beutelspacher, H. Fazekasova, A.K.M. Shamsul Alam, M. O. McClure, and A. J.T. George Effect of Vectors on Human Endothelial Cell Signal Transduction: Implications for Cardiovascular Gene Therapy Arterioscler Thromb Vasc Biol, March 1, 2006; 26(3): 462 - 467. [Abstract] [Full Text] [PDF] S. J. Antonia, N. Mirza, I. Fricke, A. Chiappori, P. Thompson, N. Williams, G. Bepler, G. Simon, W. Janssen, J.-H. Lee, et al. Combination of p53 Cancer Vaccine with Chemotherapy in Patients with Extensive Stage Small Cell Lung Cancer Clin. Cancer Res., February 1, 2006; 12(3): 878 - 887. [Abstract] [Full Text] [PDF] P. H. Tan, J. B. Yates, S.-A. Xue, C. Chan, W. J. Jordan, J. E. Harper, M. P. Watson, R. Dong, M. A. Ritter, R. I. Lechler, et al. Creation of tolerogenic human dendritic cells via intracellular CTLA4: a novel strategy with potential in clinical immunosuppression Blood, November 1, 2005; 106(9): 2936 - 2943. [Abstract] [Full Text] [PDF]

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