Header

UZH-Logo

Maintenance Infos

Lentiviral-mediated transcriptional targeting of dendritic cells for induction of T cell tolerance in vivo


Dresch, C; Edelmann, L S; Marconi, P; Brocker, T (2008). Lentiviral-mediated transcriptional targeting of dendritic cells for induction of T cell tolerance in vivo. Journal of Immunology, 181(7):4495-4506.

Abstract

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 DCspecific 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.

Abstract

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 DCspecific 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.

Statistics

Citations

37 citations in Web of Science®
39 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

0 downloads since deposited on 19 Jan 2009
0 downloads since 12 months

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Virology
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:1 October 2008
Deposited On:19 Jan 2009 15:55
Last Modified:05 Apr 2016 12:50
Publisher:American Association of Immunologists
ISSN:0022-1767
Publisher DOI:https://doi.org/10.4049/jimmunol.181.7.4495
PubMed ID:18802052

Download

Preview Icon on Download
Filetype: PDF - Registered users only
Size: 2MB
View at publisher