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

Abstract Aims/hypothesis. Testicular Sertoli cells protect allogeneic islet grafts from rejection after transplantation into animals with chemically induced diabetes. 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 the renal capsule of non-obese diabetic mice, alone and together with purified Sertoli cells prepared from testes of newborn non-obese diabetic mice. Additionally, we examined the composition of the islet and Sertoli cell co-transplants by immunohistochemistry to determine whether islet graft survival correlated with Sertoli cell expression of Fas ligand.?Results. Sertoli cell doses of 1, 2 and 4 × 10⁶ cells produced a dose-dependent prolongation of median islet graft survival from 11 days (islets alone) to 32 days (islets + 4 × 10⁶ Sertoli cells); addition of 8 × 10⁶ Sertoli cells to the islet grafts decreased, however, median survival to 8 days. Immunohistochemical analysis of the islet and Sertoli cell co-transplants showed a correlation between Fas ligand expression by Sertoli cells and graft infiltration by neutrophilic leucocytes, leading to islet beta-cell destruction and diabetes recurrence.?Conclusion/interpretation. Sertoli cells exert opposing effects on survival of syngeneic islet grafts in non-obese diabetic mice: Fas ligand-dependent neutrophil infiltration and graft destruction, and Fas ligand-independent protection of the graft from autoimmune destruction. [Diabetologia (2000) 43: 474–480] Received: 13 December 1999 and in revised form: 20 January 2000