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* Institute for Immunology, Ludwig-Maximilians-University, Munich, Germany; and
Department of Experimental and Diagnostic Medicine, University of Ferrara, Ferrara, Italy
Dendritic cells (DCs) are important APCs able to induce both tolerance and immunity. Therefore, DCs are attractive targets for immune intervention. However, the ex vivo generation and manipulation of DCs at sufficient numbers and without changing their original phenotypic and functional characteristics are major obstacles. To manipulate DCs in vivo, we developed a novel DC-specific self-inactivating lentiviral vector system using the 5' untranslated region from the DC-STAMP gene as a putative promoter region. We show that a gene therapy approach with these DC-STAMP-lentiviral vectors yields long-term and cell-selective transgene expression in vivo. Furthermore, transcriptionally targeted DCs induced functional, Ag-specific CD4 and CD8 T cell tolerance in vivo, which could not be broken by viral immunization. Tolerized CTL were unable to induce autoimmune diabetes in a murine autoimmune model system. Therefore, delivering transgenes specifically to DCs by using viral vectors might be a promising tool in gene therapy.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by a grant from the Deutsche Forschungsgemeinschaft Sonderforschungsbereich 455 (to T.B.), the FP6 from the European Commission (EU-Herpesvirus-based vaccines against Rotavirus infections to T.B. and P.M.), and the Brazilian Ministry of Education Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Foundation (to C.D.).
2 C.D. and S.L.E. contributed equally to this manuscript.
3 Current address: Institute of Virology, University of Zurich, Zurich, Switzerland.
4 Address correspondence and reprint requests to Dr. Thomas Brocker, Institute for Immunology, Ludwig-Maximilians-University, Goethestrasse 31, D-80336 Munich, Germany. E-mail address: brocker{at}lmu.de
5 Abbreviations used in this paper: DC, dendritic cell; SIN, self inactivating; eGFP, enhanced GFP; MOI, multiplicity of infection; HSC, hematopoietic stem cell; BM, bone marrow; RIP, rat insulin promoter; gB, glycoprotein B.
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