Tolerance in heart transplantation: the Holy Grail, or an attainable goal?

The father of cardiac transplantation, Norman Shumway, famously predicted that tolerance was the future of the field, and always would be. Although his prediction remains true to date, significant progress has been made toward this goal, the "Holy Grail" for transplant clinicians. Current efforts are fueled by disappointing long-term outcomes associated with chronic immunosuppression, and the promise that partial or complete tolerance will impact long-term results favorably. This article provides a clinical definition of tolerance primarily based on lessons learned from animal heart allograft models. It reviews several promising strategies for inducing tolerance and detecting its presence through the use of biomarkers in peripheral blood or the graft, and outlines a possible path toward making this vision a clinical reality.