Sequential transplantation induces islet allograft tolerance.

Liver transplantation (LT) in some rat strain combinations can induce tolerance to other organ grafts of liver donor strain. The aim of the study was to examine the effect of LT on islet allografts. Islets were isolated by collagenase digestion and purified by dextran-gradient separation. Islets from two donor animals (>2,000) were transplanted under the left kidney capsule of streptozotocin-induced diabetic rats. The liver was implanted orthotopically. The results showed that concurrent LT and islet transplantation (IT) prolonged survival of islet allografts modestly, but islet allografts survived indefinitely when LT was performed before or after IT. LT delayed or reversed ongoing islet graft rejection. IT could trigger rejection in otherwise tolerated liver grafts. We conclude that sequential IT-LT or LT-IT can induce islet allograft tolerance or liver rejection and that the mechanisms involved may differ from those involved with LT simultaneously with either IT or vascularized organ grafts. Copyright 2001 Wiley-Liss, Inc.