The effect of FasL expression on pancreatic islet allografts
Zhan, W.; Cai, S.; Wang, J.; He, Y.; Zheng, Z.; Peng, J.
Chinese Medical Journal 115(7): 1006-1009
2002
ISSN/ISBN: 0366-6999 PMID: 12150731 Document Number: 551949
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 X 107, 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 < 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.