Induction of primary anti-HIV CD4 and CD8 T cell responses by dendritic cells transduced with self-inactivating lentiviral vectors |
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Authors: | Chen Xiaochuan Wang Bei Chang Lung-Ji |
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Affiliation: | Department of Molecular Genetics and Microbiology, Powell Gene Therapy Center, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL 32610-0266, USA. |
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Abstract: | In this study, we demonstrate that a minimal self-inactivating (SIN) lentiviral vector (LV) that does not encode any human immunodeficiency virus (HIV) genes is able to induce HIV-specific CD4 and CD8 T cell responses after transduction of dendritic cells (DCs). The LV-DC-primed T cells displayed HIV-specific lytic degranulation, as illustrated by acquisition of CD107a/b expression on the cell surface and up-regulation of active caspase 3. HIV-specific cytotoxic T lymphocyte (CTL) response was consistently detected using different assays, and T cell receptors specific to three prominent HIV epitopes, SL9 (Gag peptide: SLYNTVATL), IV9 (Pol peptide: ILKEPVHGV), and MA10 (In peptide: MASDFNLPPV) were detected using HLA-A0201 peptide-tetramers. These results demonstrate that DCs transduced with the minimal SIN-LV can efficiently induce HIV-specific CD4 and CD8 T cell responses. Since LVs are popular gene transfer tools, our results have fundamental implications for future LV applications and DC vaccine development. |
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Keywords: | Lentiviral vectors Dendritic cells HIV Vaccine |
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