FAS LIGAND GENE TRANSFER TO RENAL ALLOGRAFTS IN RATSEffects on Allograft Survival1,2
作者:
Swenson3,4 Kim,
Ke3 Bibo,
Wang3 Tao,
Markowitz3 Jay,
Maggard3 Melinda,
Spear5 Gerald,
Imagawa3 David,
Goss3 John,
Busuttil3 Ronald,
Seu3,6 Philip,
期刊:
Transplantation
(OVID Available online 1998)
卷期:
Volume 65,
issue 2
页码: 155-160
ISSN:0041-1337
年代: 1998
出版商: OVID
数据来源: OVID
摘要:
Background.Fas ligand (FasL) induces apoptosis of cells bearing its receptor Fas, and has been shown to be important in T-cell development and regulation and in immune privilege. We hypothesized that FasL expression by renal allografts might provide protection from rejection.Methods.The murine FasL cDNA was cloned into a replication-defective adenovirus (AdV-FasL). Protein expression was confirmed by immunostaining of AdV-FasL-transduced HeLa cells. Allogeneic kidney transplants were performed between WF (RT1u) donors and Lewis(RT1) recipients. Donor kidneys were perfused in situ with saline alone (control), or 9×109plaqueforming units of AdV-FasL. One native kidney was removed at the time of transplant and the other at 6 or 7 days. Uremic death was the endpoint, and deaths within 7 days of transplant were excluded. Transduced allografts were stained for FasL expression using a monoclonal antibody and tested for FasL mRNA production by reverse transcriptase-polymerase chain reaction and Northern blotting.Results.Immunostaining of AdV-FasL-transduced allografts demonstrated efficient gene transfer lasting approximately 2 weeks, and FasL mRNA production in the AdV-FasL-transduced allografts was confirmed by Northern blotting and reverse transcriptase-polymerase chain reaction. Mean survival of animals with AdV-FasL-transduced renal allografts was 27.8 days vs. 11.6 days in control animals (P<0.05).Conclusions.(1) Adenoviral vectors can successfully transduce rat kidneys with the FasL cDNA. (2) FasL gene transfer prolongs rat renal allograft survival.
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