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Dendritic cell functional improvement in a preclinical model of lentiviral-mediated gene therapy for Wiskott–Aldrich syndrome

Gene Therapy volume 19, pages 1150–1158 (2012)Cite this article

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Abstract

Wiskott–Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency caused by the defective expression of the WAS protein (WASP) in hematopoietic cells. It has been shown that dendritic cells (DCs) are functionally impaired in WAS patients and was−/− mice. We have previously demonstrated the efficacy and safety of a murine model of WAS gene therapy (GT), using stem cells transduced with a lentiviral vector (LV). The aim of this study was to investigate whether GT can correct DC defects in was−/− mice. As DCs expressing WASP were detected in the secondary lymphoid organs of the treated mice, we tested the in vitro and in vivo function of bone marrow-derived DCs (BMDCs). The BMDCs showed efficient in vitro uptake of latex beads and Salmonella typhimurium. When BMDCs from the treated mice (GT BMDCs) and the was−/− mice were injected into wild-type hosts, we found a higher number of cells that had migrated to the draining lymph nodes compared with mice injected with was−/− BMDCs. Finally, we found that ovalbumin (OVA)-pulsed GT BMDCs or vaccination of GT mice with anti-DEC205 OVA fusion protein can efficiently induce antigen-specific T-cell activation in vivo. These findings show that WAS GT significantly improves DC function, thus adding new evidence of the preclinical efficacy of LV-mediated WAS GT.

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Acknowledgements

This work was supported by grants from Italian Telethon Foundation to AV, Telethon Grant GGP06267 to FB, and Ministero della Salute RF 2007-2008 Giovani Ricercatori Grant (to MB).

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Authors and Affiliations

  1. Vita-Salute San Raffaele University, Milan, Italy

    M Catucci & M G Roncarolo

  2. San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milan, Italy

    M Catucci, M Bosticardo, M C Castiello, E Draghici, M Locci, M G Roncarolo, A Aiuti & A Villa

  3. International Centre for Genetic Engineering and Biotechnology, Padriciano, Italy

    F Prete & F Benvenuti

  4. School of Medicine, University of Rome ‘Tor Vergata’, Rome, Italy

    A Aiuti

  5. UOS Milano, IRGB CNR, Milan, Italy

    A Villa

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  1. M Catucci
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Correspondence to A Villa.

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Catucci, M., Prete, F., Bosticardo, M. et al. Dendritic cell functional improvement in a preclinical model of lentiviral-mediated gene therapy for Wiskott–Aldrich syndrome. Gene Ther 19, 1150–1158 (2012). https://doi.org/10.1038/gt.2011.202

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