Clinical transplantation tolerance: many rivers to cross

Modern immunosuppressive regimens for organ transplantation have resulted in excellent short-term results but less dramatic improvements in long-term outcomes. Moreover, they are associated with significant deleterious effects. One solution that should avoid the adverse drug effects and result in improved graft and patient longevity as well as positively impacting on the organ shortage is the establishment of transplantation tolerance. Ever since the original description of transplantation tolerance in rodent allografts, there have been significant efforts made to translate tolerance-promoting strategies to the clinical arena. However, >50 years later, we are still faced with significant barriers that are preventing such a goal from being widely attained. Nonetheless, pilot clinical tolerance protocols are underway in selected transplant recipients. In this review, we discuss the scientific and nonscientific issues that must be overcome for successful transplantation tolerance to become a clinical reality.