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Journal of Virology, March 2002, p. 2899-2911, Vol. 76, No. 6
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.6.2899-2911.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Distinct Roles of Adenovirus Vector-Transduced Dendritic Cells, Myoblasts, and Endothelial Cells in Mediating an Immune Response against a Transgene Product

Stéphanie Mercier,1 Hanne Gahéry-Segard,2 Martine Monteil,1 Renée Lengagne,2 Jean-Gérard Guillet,2 Marc Eloit,1 and Caroline Denesvre1*

UMR INRA 955, Génétique Moléculaire et Cellulaire, Génétique Virale, Ecole Nationale Vétérinaire d'Alfort, 94704 Maisons-Alfort Cédex,1 Laboratoire d'Immunologie des Pathologies Infectieuses et Tumorales, INSERM Unité 44527, Institut Cochin de Génétique Moléculaire, Université R. Descartes, Hôpital Cochin, 75014 Paris, France2

Received 8 November 2001/ Accepted 13 December 2001

Adenovirus-mediated gene delivery via the intramuscular route efficiently promotes an immune response against the transgene product. In this study, a recombinant adenovirus vector encoding ß-galactosidase (AdßGal) was used to transduce dendritic cells (DC), which are antigen-presenting cells, as well as myoblasts and endothelial cells (EC), neither of which present antigens. C57BL/6 mice received a single intramuscular injection of AdßGal-transduced DC, EC, or myoblasts and were then monitored for anti-ß-galactosidase (anti-ß-Gal) antibody production, induction of gamma interferon-secreting CD8+ T cells, and protection against melanoma tumor cells expressing ß-Gal. While all transduced cell types were able to elicit an antibody response against the transgene product, the specific isotypes were distinct, with exclusive production of immunoglobulin G2a (IgG2a) antibodies following injection of transduced DC and EC versus equivalent IgG1 and IgG2a responses in mice inoculated with transduced myoblasts. Transduced DC induced a strong ex vivo CD8+ T-cell response at a level of 50% of the specific response obtained with the AdßGal control. In contrast, this response was 6- to 10-fold-lower in animals injected with transduced myoblasts and EC. Accordingly, only animals injected with transduced DC were protected against a ß-Gal tumor challenge. Thus, in order to induce a strong and protective immune response to an adenovirus-encoded transgene product, it is necessary to transduce cells of dendritic lineage. Importantly, it will be advantageous to block the transduction of DC for adenovirus-based gene therapy strategies.

* Corresponding author. Present address: Pathologie Aviaire et Parasitologie, INRA Centre de Tours, 37380 Nouzilly, France. Phone: 33 2 47 42 79 85. Fax: 33 2 47 42 77 74. E-mail: denesvre{at}tours.inra.fr.

Journal of Virology, March 2002, p. 2899-2911, Vol. 76, No. 6
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.6.2899-2911.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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