Modulation of human dendritic-cell function following transduction with viral vectors: implications for gene therapy
| Autor: | Myra O. McClure, Giovanna Lombardi, Hans J. Stauss, Peter Mitchell, Mary A. Ritter, D. Frank P. Larkin, Yaohe Wang, Sven C. Beutelspacher, Shao-An Xue, Peng H. Tan, Andrew J.T. George, James C. McAlister |
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| Rok vydání: | 2005 |
| Předmět: |
viruses
Genetic Vectors Immunology chemical and pharmacologic phenomena Biology Biochemistry Virus Adenoviridae Viral vector Proinflammatory cytokine Transduction (genetics) Transduction Genetic Interferon medicine Humans Antigen-presenting cell Cells Cultured Inflammation Lentivirus Tryptophan Dendritic Cells Genetic Therapy Cell Biology Hematology Dendritic cell Th1 Cells Mixed lymphocyte reaction Up-Regulation Phenotype Cytokines Interferons Lymphocyte Culture Test Mixed Signal Transduction medicine.drug |
| Zdroj: | Blood. 105:3824-3832 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2004-10-3880 |
| Popis: | 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 anemia virus (EIAV), and Moloney murine leukemia virus (MMLV) all up-regulate costimulatory molecules and major histocompatibility complex (MHC) class II expression on DCs, as well as, in the case of Ad and lentiviral vectors, inducing production of Th1 and proinflammatory cytokines. Following transduction there is activation of double-stranded (ds) RNA-triggered pathways resulting in interferon (IFN) α/β 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 mDCs results in up-regulation of the indoleamine 2,3-dioxygenase (IDO) enzyme, which down-regulates T-cell responsiveness. Inhibition of IDO restores the ability of mDCs to stimulate an 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 DCs. |
| Databáze: | OpenAIRE |
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