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Blood, 1 November 2006, Vol. 108, No. 9, pp. 2972-2978. Prepublished online as a Blood First Edition Paper on June 29, 2006; DOI 10.1182/blood-2006-03-010900. This Article Full Text (PDF) All Versions of this Article: blood-2006-03-010900v1 108/9/2972    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Marodon, G. Articles by Klatzmann, D. Search for Related Content PubMed PubMed Citation Articles by Marodon, G. Articles by Klatzmann, D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 17, 2006 Accepted June 15, 2006 Induction of antigen-specific tolerance by intrathymic injection of lentiviral vectors Gilles Marodon, Sylvain Fisson, Beatrice Levacher, Monique Fabre, Benoit L Salomon, and David Klatzmann* Universite Pierre et Marie Curie-Paris6 (UPMC), UMR 7087, Hopital de La Pitie-Salpetriere, Paris Departement de Pathologie, Universite de Medecine Paris-Sud, Hopital de Bicetre, France * Corresponding author; email: david.klatzmann{at}chups.jussieu.fr. Immune tolerance to self-antigens is established during lymphocyte differentiation in the thymus. A simple mean to induce antigen-specific tolerance in the thymus is however still elusive. We show here that intrathymic injection of a lentiviral vector expressing the hemagglutinin antigen (HA) in TCR-HA transgenic mice resulted in negative selection of HA-specific effector T-cells and sustained positive selection of HA-specific regulatory T-cells (Treg). This positive selection increased the number of HA-specific Treg by ten-fold and was comparable to the one observed in TCR-HA transgenic mice crossed with transgenic mice expressing HA under the control of the insulin promoter (Ins-HA). HA expression by radioresistant thymic epithelial cells was sufficient to drive Treg generation. Intrathymic injection of the lentiviral vector also resulted in an enrichment of HA-specific Treg cells in peripheral lymphoid organs, which prevented diabetes induced in Ins-HA mice by transfer of HA-specific effector T-cells. In this model, HA-specific Treg cells inhibited effector T-cell division in pancreatic lymph nodes. Finally, we show that intrathymic injection of a lentiviral vector expressing preproinsulin-2 could reduce the occurrence of spontaneous diabetes in non-obese diabetic mice. Intrathymic gene transfer using lentiviral vectors thus offers new means to manipulate antigen-specific tolerance. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Yu, C. L. Haymaker, R. D. Divekar, J. S. Ellis, J. Hardaway, R. Jain, D. M. Tartar, C. M. Hoeman, J. A. Cascio, A. Ostermeier, et al. Fetal Exposure to High-Avidity TCR Ligand Enhances Expansion of Peripheral T Regulatory Cells J. Immunol., July 1, 2008; 181(1): 73 - 80. [Abstract] [Full Text] [PDF]

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