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The effect of FasL gene transfer to islet cells on pancreatic islet allografts


   OBJECTIVE: To investigate the effect of FasL gene transfer to islet cells on pancreatic islet allografts.METHODS: A recombinant and replication-deficient type-5 adenovirus encoding murine FasL (AdV-FasL) was constructed by the method of calcium phosphate precipitation. Pancreatic islets were infectedwith the recombinant adenovirus AdV-FasL, and transplanted into diabetic recipients. FasL expressionwas detected by RT-PCR and immunohistochemistry. The survival of allografts and the apoptosis of genetransferred islet allografts were analyzed.RESULTS: All animals receiving islet allograft alone returned to a diabetic state by several days (meansurvival time 6.3±0.6 days). Compared with the control group, no delayed rejection and prolongedsurvival of allografts were observed in the group of FasL gene transfer. The rejection was accelerated andthe allograft survival was shortened to 3.4±0.2 days (P<0.05). Pancreatic islets infected with AdV-FasL demonstrated positive staining of FasL at 24 h, with an increased intensity at 48 h, but not inAdV-5 infected or uninfected islets. TUNEL labeling of pancreatic islet allografts at 24, 48 h revealedapoptosis that was not in AdV-5 infected allografts.CONCLUSIONS: Though co-transplantation of FasL-expressing testicular cells can induce privilege ofislet allografts and prolong allograft survival, direct expression of FasL on islet allografts infected withAdV-FasL may accelerate islets rejection by islet apoptosis and granulocyte infiltration.……