Peer-Reviewed Journal Details
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Gong, N,Pleyer, U,Volk, HD,Ritter, T
2007
March
Gene Therapy
Effects of local and systemic viral interleukin-10 gene transfer on corneal allograft survival
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transplantation cornea immunomodulation vIL-10 adenovirus liposomes TUMOR-NECROSIS-FACTOR HUMORAL IMMUNE-RESPONSES RECOMBINANT ADENOVIRUS ENDOTHELIAL-CELLS EXPRESSION CYTOKINE IL-10 REJECTION THERAPY TRANSPLANTATION
14
484
490
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 prerequisite for the success of cytokine gene therapy.
DOI 10.1038/sj.gt.3302884
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