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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Inmunología hepatitis virales > DA - CIMA - Terapia génica y Hepatología - Inmunología hepatitis virales - Artículos de revista >

Enhanced T cell responses against hepatitis C virus by ex vivo targeting of adenoviral particles to dendritic cells
Authors: Echeverria, I. (Itziar)
Pereboev, A. (Alexander)
Silva, L. (Leyre)
Zabaleta, A. (Aintzane)
Riezu-Boj, J.I. (José Ignacio)
Bes, M. (Marta)
Cubero, M. (María)
Borras-Cuesta, F. (Francisco)
Lasarte, J.J. (Juan José)
Esteban, J.I. (Juan Ignacio)
Prieto, J. (Jesús)
Sarobe, P. (Pablo)
Keywords: Adenoviridae/physiology
Dendritic Cells/virology
Hepacivirus/immunology
Hepatitis C/immunology
T-Lymphocytes, Helper-Inducer/physiology
Issue Date: 2011
Publisher: Wiley Blackwell
Publisher version: http://dx.doi.org/10.1002/hep.24325
ISSN: 0270-9139
Citation: Echeverria I, Pereboev A, Silva L, Zabaleta A, Riezu-Boj JI, Bes M, et al. Enhanced T cell responses against hepatitis C virus by ex vivo targeting of adenoviral particles to dendritic cells. Hepatology 2011 Jul;54(1):28-37.
Abstract
Injection of dendritic cells (DCs) presenting viral proteins constitutes a promising approach to stimulate T cell immunity against hepatitis C virus (HCV). Here we describe a strategy to enhance antigen loading and immunostimulatory functions of DCs useful in the preparation of therapeutic vaccines. Incubation of murine DCs with CFm40L, an adapter molecule containing the coxsackie-adenovirus receptor fused to the ecto-domain of murine CD40L-induced DC maturation, produced high amounts of interleukin-12 and up-regulation of molecules associated with T helper 1 responses. Accordingly, targeting of an adenovirus encoding HCV NS3 protein (AdNS3) to DCs with CFm40L strongly enhanced NS3 presentation in vitro, activating interferon-γ-producing T cells. Moreover, immunization of mice with these DCs promoted strong CD4 and CD8 T cell responses against HCV NS3. CFh40L, a similar adapter molecule containing human CD40L, enhanced transduction and maturation of human monocyte-derived DCs. Comparison of DCs transduced with AdNS3 and CFh40L from patients with chronic HCV infection and healthy donors revealed similar maturation levels. More importantly, DCs from the patients induced NS3-specific responses when transduced with AdNS3 and CFh40L but not with AdNS3 alone. CONCLUSION: DCs transduced with AdNS3 and the adapter molecule CFm/h40L exhibit enhanced immunostimulatory functions, induce robust anti-HCV NS3 immunity in animals, and can induce antiviral immune responses in subjects with chronic HCV infection. This strategy may serve as therapeutic vaccination for patients with chronic hepatitis C.
Permanent link: http://hdl.handle.net/10171/20361
Appears in Collections:DA - CUN - Medicina interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Virología - Artículos de revista
DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología experimental - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología hepatitis virales - Artículos de revista

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