Low-temperature culture of human islets or in vivo treatment with L3T4 antibody produces a marked prolongation of islet human-to-mouse xenograft survival

Abstract

In previous studies we have shown that rejection of islet xenografts transplanted between closely related species (rat to mouse) can be prevented by destruction or alteration of antigen-presenting cells in the donor islets and temporary immunosuppression of the recipients. Relatively few studies have been reported on the survival of islet xenografts transplanted between widely discordant species. In the present study, isolated human islets were transplanted beneath the renal capsule of B6 mice made diabetic by the injection of streptozotocin. The effect of culturing the human islets at 24 degrees C for 7 days with or without the administration of anti-L3T4 for 7 days after transplantation was determined. A marked prolongation of the mean survival time was obtained with low-temperature culture alone (greater than 40.2 +/- 9.9 days), with anti-L3T4 alone (greater than 45.2 +/- 6.3 days), and with the combination of these regimens (greater than 51.9 +/- 5.1 days) as compared to controls (7.5 +/- 1.1 days). The surprising finding was the marked effect of low-temperature culture alone on prolonging human islet xenograft survival because this treatment of the donor islets had no effect on the survival of rat islet xenografts. Intact human islets were present in approximately equal to 80% of the recipients after returning to a diabetic state, whereas xenografts of rat islets were completely destroyed. The findings indicate that complete rejection of islets across this widely discordant species barrier is slower than across a closely related barrier and may be occurring by a different rejection process.