Clinical islet transplantation: where immunity and metabolism intersect?

The dramatic results of the Edmonton Protocol in 2000 triggered tremendous excitement over the application of pancreatic islet transplantation as a viable approach to achieving consistent insulin independence in type 1 diabetic patients. However, this optimism in the field was tempered by follow-up studies showing frequent attrition of graft function commonly requiring a return to exogenous insulin therapy within 1-3 years after transplant. The purpose of this review is to put these initial studies in perspective and to highlight progress and challenges in this important field.

Recent clinical and experimental findings demonstrate a progressive improvement in the function and durability of islet allografts. Induction therapies targeting T lymphocytes and costimulatory pathways have been highly effective at promoting islet transplant function. It is also apparent that islet injury associated with metabolic distress provides a nonimmune barrier to islet transplant outcomes.

Newer therapeutic interventions show great promise for attenuating the adaptive immune response to islet allografts. Also, clarifying the mechanisms of metabolic-related tissue distress may provide additional potential targets for improving islet graft outcomes.