Identification of tolerant recipients following liver transplantation

The need to administer livelong immunosuppressive medication (IS) to transplant recipients to prevent graft rejection often results in severe side effects like infections, malignancies, renal failure and cardiovascular complications. This constitutes one of the major drawbacks of clinical organ transplantation. Therefore, a means to establish medication-independent graft acceptance (tolerance) would be a major breakthrough in the field. Transplantation tolerance can be readily generated in experimental animal models, but so far most efforts to purposely induce this phenomenon in the clinic have failed. Liver transplantation is a unique clinical setting in that up to 20% of recipients can spontaneously withdraw IS without rejecting their grafts and are considered as operationally tolerant. This clinical observation is probably the most extreme manifestation of the well-documented intrinsic tolerogenic properties of the liver. The high rate of spontaneous operational tolerance following liver transplantation and the relative resistance of liver allografts to the effects of cytopathic alloimmune responses make liver transplantation the most suitable clinical transplantation model to test IS withdrawal strategies and tolerance promoting therapies. Liver transplantation constitutes therefore a unique setting to learn the mechanisms underlying allograft tolerance in humans.