Fetal pancreas transplantation in non-obese diabetic (NOD) mice. A comparison of iso-, allo- and xenografts.
Prediabetic NOD/Wehi male mice aged 100 days were each transplanted under the renal capsule with three pieces of organ-cultured fetal pancreas; an isograft of NOD pancreas, an allograft of CBA (H-2k) pancreas, and a xenograft of fetal pig tissue. Groups of mice were given immunosuppression on days -1, 0 and +1 relative to transplantation with either an anti-CD4 monoclonal antibody (MAb, GK1.5), with or without a low dose (50 mg/kg IP) of cyclosporin A (CsA), with CsA alone or phosphate buffered saline in non-immunosuppressed controls. Flow cytometric analysis showed that CD4+ cells were severely depleted in mice that had been given GK1.5 11 days previously, but these cells slowly recovered to 35% of control levels by day 28, and 70% by day 56. The xenografted islets were slowly destroyed in the MAb-treated mice, at a rate which was slower than rejection of the allografts. At 28 days, when the allografts were severely affected, the xenografts were generally well preserved. The immunosuppression also did not stop mononuclear cell infiltration of the isografts. However, by 56 days all xenografts and most allografts were totally destroyed, and the isografts were infiltrated to an extent similar to that present in the pancreas. These results suggest that xenogeneic islets are no more and possibly even less immunogeneic than MHC-mismatched allografts, and are only slowly rejected after a peri-transplant period of immunosuppression used to transiently deplete CD4+ cells. However, the transient immunisuppression used did not result in indefinite xenograft survival suggestive of immunological tolerance.