Fas配体表达对同种胰岛移植的影响

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±0.56)?d.与胰岛细胞同时移植的睾丸细胞数增加至1×107时,存活期大于50?d(P＜0.05).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±0.24)?d.FasL转染的胰岛细胞在移植后24h见FasL表达,48h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.

Effects of Fas ligand expression on pancreatic islet allografts

OBJECTIVE: To investigate the immune privilege of islet allgrafts induced by the Fas ligand (FasL) expressed by co-transplanted testicular Sertoli cells and the effects of FasL gene transfected into islet cells on pancreatic islet allografts. METHODS: The allogeneic islets and testicular cells from rats were co-transplanted into diabetic recipients. Pancreatic islet cells were firstly infected with the recombinant adenovirus AdV-FasL and then transplanted into the diabetic recipients. Allograft survival, islet function and apoptosis of infiltrative lymphocytes in allografts and gene-transfected islet allografts were observed. RESULTS: All the animals receiving islet allografts alone returned to a diabetic status in several days (mean survival time = 6.3 +/- 0.56 days). When the number of testicular cells co-transplanted with islets increased to 1 x 10(7), all the animals remained normoglycemic throughout the follow-up period (P < 0.05). Sertoli cells expressing FasL induced apoptosis of infiltrative lymphocytes in the allografts. In the group of FasL gene transfection, the rejection of allografts was accelerated and the allograft survival time shortened to 3.4 +/- 0.24 days (P < 0.05). Pancreatic islets infected with AdV-FasL demonstrated positive staining for FasL at the 24th hour and increased intensity at the 48th hour after transplantation. After the transplantation, apoptosis of FasL-transfected islet cells occurred. CONCLUSIONS: Co-transplantation of testicular Sertoli cells expressing FasL and islets can induce apoptosis of activated lymphocytes and allows long-term survival of allogeneic islets because of immune privilege. However, direct expression of FasL by islet allografts infected with AdV-FasL accelerates the islet rejection by islet cell apoptosis and granulocytic infiltration.