The future of organ transplantation: from the laboratory to the clinic

This is a short review of tolerance from the point of view of the clinician. Various examples of tolerance occurring in patients and animal models that relate to the clinical experience are described. It is suggested that there may be different mechanisms by which tolerance is achieved, but from the patient's point of view operational tolerance is the goal, whereby, after a short induction procedure, the patient will maintain good function in the grafted organ indefinitely without maintenance immunosuppression. It is pointed out that such a goal may be difficult to achieve with any given protocol due to the enormous variation between donors and recipients of organ grafts of tissue matching, innate immune reactivity and susceptibility to disturbance of a tolerant state by infections or allergic reactions. Thus the case is made for prope or almost tolerance in which graft acceptance is maintained by a low, non-toxic dosage of maintenance immunosuppression that may not be required indefinitely.