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Tolerance of activated pathogenic CD4+ T cells by transcriptional targeting of dendritic cells

Gene Therapy volume 22, pages 382–390 (2015)Cite this article

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Abstract

We have recently shown that targeted expression of myelin oligodendrocyte glycoprotein (MOG) to dendritic cells with self-inactivating-lentivirus vectors induces antigen-specific tolerance in naive antigen-specific CD4+ T cells and protects mice from experimental autoimmune encephalomyelitis (EAE). In the present study, we demonstrate that this approach also induces tolerance of activated antigen-specific CD4+ T cells and completely protects mice from passive EAE induction. Tolerance induction did not correlate with the depletion of the preactivated antigen-specific CD4+ T cells. However, upon isolation and in vitro re-stimulation at day 6 after adoptive transfer the MOG-specific CD4+ T cells from the non-tolerized mice produced large amounts of inflammatory cytokines, whereas those from tolerized mice did not. This unresponsiveness correlated with the upregulation of regulatory molecules associated with anergy and regulatory T cells (Tregs). The in vivo depletion of Tregs resulted in EAE susceptibility of the tolerized animals, suggesting that these cells have indeed a role in tolerance induction/maintenace.

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Acknowledgements

We thank Judith Robotka and Carla Rohrer-Bley for technical support and Dana Salathe for assistance with mice. This work was supported by funds from the Swiss Multiple Sclerosis Society and the University of Zurich.

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Author notes

  1. C Dresch

    Present address: 2Present address: Department of Immunology, University of Washington, Seattle, WA, USA.,

  2. C Dresch and C Fraefel: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Virology, University of Zürich, Zürich, Switzerland

    B de Andrade Pereira, M Ackermann, S Chaudhary, R Vogel, B Vogt, C Dresch & C Fraefel

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  1. B de Andrade Pereira
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Correspondence to C Fraefel.

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de Andrade Pereira, B., Ackermann, M., Chaudhary, S. et al. Tolerance of activated pathogenic CD4+ T cells by transcriptional targeting of dendritic cells. Gene Ther 22, 382–390 (2015). https://doi.org/10.1038/gt.2015.6

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