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

Hepatobiliary & Pancreatic Diseases International 2003年第2期2卷 624-628页

作者： Shi-Rong Cai Yu-Long He Mei-Jin Huang Jun-Sheng Peng Jian-Ping Wang Wen-Hua Zhan the Department of Gastrointestinal and Pancreatic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China Department of Gastrointestinal and Pancreatic Surgery First Affiliated Hospital Sun Yat-Sen University Guangzhou 510080 China.

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 infected with the recombinant adenovirus AdV-FasL, and transplanted into diabetic recipients. FasL expression was detected by RT-PCR and immunohistochemistry. The survival of allografts and the apoptosis of gene transferred islet allografts were analyzed. RESULTS: All animals receiving islet allograft alone returned to a diabetic state by several days (mean survival time 6.3±0.6 days). Compared with the control group, no delayed rejection and prolonged survival of allografts were observed in the group of FasL gene transfer. The rejection was accelerated and the allograft survival was shortened to 3.4±0.2 days (Pislets infected with AdV- FasL demonstrated positive staining of FasL at 24 h, with an increased intensity at 48 h, but not in AdV-5 infected or uninfected islets. TUNEL labeling of pancreatic islet allografts at 24, 48 h revealed apoptosis that was not in AdV-5 infected allografts. CONCLUSIONS: Though co-transplantation of FasL-expressing testicular cells can induce privilege of islet allografts and prolong allograft survival, direct expression of FasL on islet allografts infected with AdV-FasL may accelerate islets rejection by islet apoptosis and granulocyte infiltration.

关键词： islet/transplantation Fas ligand immune privilege gene therapy

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