Testicular Sertoli cells exert both protective and destructive effects on syngeneic islet grafts in non-obese diabetic mice

Citation
Gs. Korbutt et al., Testicular Sertoli cells exert both protective and destructive effects on syngeneic islet grafts in non-obese diabetic mice, DIABETOLOG, 43(4), 2000, pp. 474-480
Citations number
35
Categorie Soggetti
Endocrynology, Metabolism & Nutrition","Endocrinology, Nutrition & Metabolism
Journal title
DIABETOLOGIA
ISSN journal
0012186X → ACNP
Volume
43
Issue
4
Year of publication
2000
Pages
474 - 480
Database
ISI
SICI code
0012-186X(200004)43:4<474:TSCEBP>2.0.ZU;2-E
Abstract
Aims/hypothesis. Testicular Sertoli cells protect allogeneic islet grafts f rom rejection after transplantation into animals with chemically induced di abetes. The aims of this study were to determine whether Sertoli cells can protect syngeneic islets from autoimmune destruction after transplantation into non-obese diabetic (NOD) mice and, if so, whether protection is due to Sertoli cell expression of Fas ligand (FasL), believed to be the mechanism that protects against allograft rejection. Methods. We compared the survival of syngeneic islets transplanted under th e renal capsule of nonobese diabetic mice, alone and together with purified Sertoli cells prepared from testes of newborn nonobese diabetic mice. Addi tionally, we examined the composition of the islet and Sertoli cell co-tran splants by immunohistochemistry to determine whether islet graft survival c orrelated with Sertoli cell expression of Fas ligand. Results. Sertoli cell doses of 1, 2 and 4 x 10(6) cells produced a dose-dep endent prolongation of median islet graft survival from 11 days (islets alo ne) to 32 days (islets + 4 x 10(6) Sertoli cells); addition of 8 x 10(6) Se rtoli cells to the islet grafts decreased, however, median survival to 8 da ys. Immunohistochemical analysis of the islet and Sertoli cell co-transplan ts showed a correlation between Fas ligand expression by Sertoli cells and graft infiltration by neutrophilic leucocytes, leading to islet beta-cell d estruction and diabetes recurrence. Conclusion/interpretation. Sertoli cells exert opposing effects on survival of syngeneic islet grafts in nonobese diabetic mice: Fas ligand-dependent neutrophil infiltration and graft destruction, and Fas ligand-independent p rotection of the graft from autoimmune destruction.