Immunology of pancreatic islet transplantation

Abstract

Clinical protocols in type 1 diabetic patients to optimize islet survival and function post-transplantation improved dramatically in the last decade, but it is clear that this approach still has potential limitations to provide long term insulin independency. Islet allografts administered in the liver via the portal vein are exposed to several factors contributing to a rapid loss of function that may reach 50% of the initial beta cell mass. Allo- and auto-immune reactions - an unique situation in clinical transplantation - are partially overcome with immunosuppressive regimen. Serological markers and T cell reactivities may correlate with graft failure. Most of the drugs that are used, including rapamycin (sirolimus) or the calcineurin inhibitor tacrolimus (FK506), have deleterious effects on beta function and/or insulin sensitivity. Immediate factors that limit initial islet engraftment have been elucidated, including instant blood mediated inflammatory reaction and angiogenesis. Newer interventions designed to promote islet survival, to prevent apoptosis, to promote islet growth and to protect islets in the long run from immunological injury are rapidly approaching clinical trials.