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Effects of local and systemic viral interleukin-10 gene transfer on corneal allograft survival

Gene Therapy volume 14, pages 484–490 (2007)Cite this article

Abstract

In this study, we explored the immunomodulatory effects of viral interleukin (IL) IL-10 after ex vivo and in vivo gene transfer in experimental corneal transplantation. Wistar–Furth rats were used as donors and major histocompatibility complex class I/II-disparate Lewis rats served as recipients. For ex vivo gene therapy donor corneas were either transfected with liposome/vIL-10 plasmid DNA mixtures or transduced with a vIL-10 expressing adenovirus vector (AdvIL-10). For in vivo studies, recipients were treated with AdvIL-10 intraperitoneally 1 day before transplantation. Graft survival was analysed using the Kaplan–Meier survival method. To monitor the efficacy of the therapy messenger RNA (mRNA) cytokine expression profiles in grafts and draining lymph nodes were analysed by quantitative real-time reverse transcription-polymerase chain reaction. Moreover, anti-adenovirus immunity was also investigated. Neither ex vivo liposome-mediated vIL-10 gene transfer nor ex vivo AdvIL-10 gene transfer led to prolonged corneal allograft survival. In contrast, corneal allograft survival was significantly prolonged in animals receiving systemic AdvIL-10 gene transfer. Moreover, only systemic vIL-10 gene therapy modulated the cytokine mRNA expression profile in draining lymph nodes. Interestingly, systemic AdvIL-10 gene transfer could not inhibit the generation of anti-adenovirus antibodies. Our data indicate systemic expression of the vIL-10 gene is required to modulate the cytokine expression profile in the draining lymph nodes, which might be a pre-requisite for the success of cytokine gene therapy.

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Acknowledgements

We thank Katrin Vogt and Sabine Jyrch for technical assistance. In addition, the authors would like to thank Dr René de Waal Malefyt, DNAX, Palo Alto, CA, USA for providing the vIL-10 plasmid (pcDSRa-BCRF1). This work was supported in part by DFG (Pl 150/14-1).

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Authors and Affiliations

  1. Department of Ophthalmology, Charité – University Medicine Berlin, Germany

    N Gong & U Pleyer

  2. Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    N Gong

  3. Institute of Medical Immunology, Charité – University Medicine Berlin, Germany

    H-D Volk & T Ritter

  4. Regenerative Medicine Institute, National University of Ireland, Galway, Ireland

    T Ritter

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  1. N Gong
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  2. U Pleyer
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Correspondence to T Ritter.

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Gong, N., Pleyer, U., Volk, HD. et al. Effects of local and systemic viral interleukin-10 gene transfer on corneal allograft survival. Gene Ther 14, 484–490 (2007). https://doi.org/10.1038/sj.gt.3302884

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