Sequential transplantation induces islet allograft tolerance

Liver transplantation (LT) in some rat strain combinations can induce toler ance 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 co llagenase digestion and purified by dextran-gradient separation. Islets fro m two donor animals (>2,000) were transplanted under the left kidney capsul e of streptozotocin-induced diabetic rats. The liver was implanted orthotop ically. The results showed that concurrent LT and islet transplantation (IT ) prolonged survival of islet allografts modestly, but islet allografts sur vived indefinitelywhen LT was performed before or after IT. LT delayed or r eversed ongoing islet graft rejection. IT could trigger rejection in otherw ise 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. (C) 2001 Wiley-Liss, Inc.