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
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.