[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.
Cai
S
S
Department of Gastrointestinal and Pancreatic Surgery, First Affiliated Hospital, Sun Yat-sen University of Medical Sciences, Guangzhou 510080, China.
Zhan
W
W
He
Y
Y
D000818:Animals; D017209:Apoptosis; D053222:Fas Ligand Protein; D015316:Genetic Therapy; D006084:Graft Rejection / Q000209:etiology / Q000517:prevention & control; D016381:Islets of Langerhans Transplantation / Q000401:mortality; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D012708:Sertoli Cells / Q000378:metabolism; D014162:Transfection; D014184:Transplantation, Homologous
D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins