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

Different doses of adenoviral vector expressing IL-12 enhance or depress the immune response to a coadministered antigen: the role of nitric oxide
Authors: Lasarte, J.J. (Juan José)
Corrales, F.J. (Fernando José)
Casares, N. (Noelia)
Lopez-Diaz-de-Cerio, A. (Ascensión)
Qian, C. (Cheng)
Xie, X. (Xiaoming)
Borras-Cuesta, F. (Francisco)
Prieto, J. (Jesús)
Keywords: Adenoviridae/genetics
Adenoviridae/immunology
Antigens, Viral/immunology
Genetic Vectors/administration & dosage
Genetic Vectors/immunology
Interleukin-12/genetics
Nitric Oxide/physiology
Issue Date: 1999
Publisher: American Association of Immunologists
Publisher version: http://jimmunol.org/content/162/9/5270
ISSN: 1550-6606
Citation: Lasarte JJ, Corrales FJ, Casares N, Lopez-Diaz de Cerio A, Qian C, Xie X, et al. Different doses of adenoviral vector expressing IL-12 enhance or depress the immune response to a coadministered antigen: the role of nitric oxide. J Immunol 1999 May 1;162(9):5270-5277.
Abstract
Joint immunization with two recombinant adenoviruses, one expressing hepatitis C virus (HCV) core and E1 proteins and another expressing IL-12 (RAdIL-12), strongly potentiates cellular immune response against HCV Ags in BALB/c mice when RAdIL-12 was used at doses of 1 x 105-1 x 107 plaque-forming units. However, cellular immunity against HCV Ags was abolished when higher doses (1 x 108 plaque-forming units) of RAdIL-12 were used. This immunosuppressive effect was associated with marked elevation of IFN-gamma and nitric oxide in the serum and increased cell apoptosis in the spleen. Administration of N-nitro-L -arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, to mice that received high doses of RAdIL-12 was lethal, whereas no apparent systemic toxicity by L -NAME was observed in those immunized with lower doses of the adenovirus. Interestingly, in mice immunized with recombinant adenovirus expressing core and E1 proteins of HCV in combination with RAdIL-12 at low doses (1 x 107 plaque-forming units), L -NAME inhibited T cell proliferation and CTL activity in response to HCV Ags and also production of Abs against adenoviral proteins. In conclusion, gene transfer of IL-12 can increase or abolish cell immunity against an Ag depending of the dose of the vector expressing the cytokine. IL-12 stimulates the synthesis of NO which is needed for the immunostimulating effects of IL-12, but apoptosis of T cells and immunosuppression ensues when IFN-gamma and NO are generated at very high concentrations.
Permanent link: http://hdl.handle.net/10171/21489
Appears in Collections:DA - CIMA - Oncología - Inmunoterapia - Artículos de Revista
DA - CIMA - Unidad de Proteómica, Genómica y Bioinformática - Artículos de revista
DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología hepatitis virales - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Hepatología bioquímica - Artículos de revista

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