Approaches to the Induction of Tolerance

Abstract Organ transplants are currently protected from rejection by treating recipients with potent immunosuppressive agents that suppress general immunity. While general immunosuppression does effectively protect allografts from acute rejection in the short term, chronic rejection presents a problem in the long term, and side effects from life-long non-specific immunosuppression can result in organ toxicity, infections, posttransplant malignancy and cardiovascular disease. To avoid the problem of needing these immunosuppressive drugs, early research from the forefathers of transplantation medicine showed us that achieving immunological tolerance is possible and clearly a worthy goal. However, fully understanding the mechanisms of tolerance and practically implementing protocols to reliably and safely induce tolerance have remained elusive. This book chapter delves into the history of tolerance research in organ transplantation and brings us to the current era of what we know about mechanisms that control tolerance. Finally, we will discuss how researchers are using this knowledge to design new protocols to induce tolerance in an attempt to reduce transplant recipient dependency on general immunosuppressive drug therapy.