Effects of local and systemic viral interleukin-10 gene transfer on corneal allograft survival.
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.
Gong
N
N
Department of Ophthalmology, Charité - University Medicine Berlin, Germany.
Pleyer
U
U
Volk
H-D
HD
Ritter
T
T
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D003315:Cornea / Q000276:immunology*; D016039:Corneal Transplantation / Q000379:methods*; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006082:Graft Enhancement, Immunologic; D006085:Graft Survival; D007267:Injections; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D008081:Liposomes; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046509:Tissue Culture Techniques; D014161:Transduction, Genetic / Q000379:methods; D014162:Transfection / Q000379:methods; D014184:Transplantation, Homologous
D000914:Antibodies, Viral; D008081:Liposomes; D012333:RNA, Messenger; D016753:Interleukin-10