The effect of FasL expression on pancreatic islet allografts

目的　探究睾丸细胞FasL表达能否对共移植的胰岛移植物提供免疫豁免作用以及胰岛细胞FasL基因转染对同种胰岛移植的影响。方法　将同种大鼠胰岛及睾丸细胞同时移植于糖尿病受体 ,重组腺病毒AdV FasL感染胰岛细胞后移植 ,观察移植物存活情况、胰岛功能 ,并检测移植物内浸润淋巴细胞以及基因转染胰岛细胞凋亡情况。结果　单纯移植胰岛组平均存活期为 (6 3± 0 6 )d。与胰岛细胞同时移植的睾丸细胞数增加至 1× 10 7时 ,存活期大于 6 0d(P <0 0 5 )。表达FasL的睾丸细胞在移植物内诱导浸润淋巴细胞凋亡。FasL基因转染组出现排斥加速 ,存活期缩短至 (3 4± 0 2 )d。FasL转染的胰岛细胞在移植后 2 4h见FasL表达 ,4 8h表达增强 ,移植后FasL转染胰岛细胞凋亡。结论　表达FasL的睾丸细胞与胰岛同时移植可诱导活化的淋巴细胞凋亡 ,使胰岛移植物获得免疫豁免、存活期延长 ,但通过FasL基因转染使胰岛细胞直接表达FasL引起胰岛细胞凋亡和粒细胞浸润 ,导致排斥加速。

The effect of FasL expression on pancreatic islet allografts

Objective To investigate the immune privilege induced by the Fas ligand (FasL) expressed by cotransplanted testicular Sertoli cells in islet allografts, and the effect of FasL gene transfection on islet cells in pancreatic islet allografts.Methods Allogeneic islets and testicular cells were cotransplanted into diabetic recipients.Pancreatic islets were infected with the recombinant adenovirus, AdV-FasL, and transplanted into diabetic recipients.Allograft survival, islet function, apoptosis of infiltrative lymphocytes in allografts and gene transfected islet allografts were analyzed.Results All animals receiving islet allograft alone returned to a diabetic state in a few days (mean survival time 6.3±0.6 days).When the quantity of testicular cells cotransplanted with islets increased to 1×10 7], all animals remained normoglycemic throughout the follow-up period (60 days).FasL expression by cotransplanted Sertoli cells induced apoptosis of activated lymphocytes. Rejection of allografts in the FasL gene transfer group was accelerated and allograft survival was shortened to 3.4±0.2 days (P&lt;0.05).Pancreatic islets infected with AdV-FasL demonstrated positive staining for FasL at 24 h after transplantation, with increased intensity at 48 h.Apoptosis assays of pancreatic islet allografts at 24 h and 48 h revealed apoptosis of transfected islets.Conclusions FasL-expressing testicular Sertoli cells can induce apoptosis of activated lymphocytes.Cotransplantation of testicular cells allows long-term survival of allogeneic islets because of immune privilege, but the direct expression of FasL on islet allografts infected with AdV-FasL accelerates islet rejection via islet apoptosis and granulocyte infiltration.