Transplantation and tolerance

Excerpt

Solid organ transplantation is the treatment of choice for many end-stage organ diseases and can be life saving for patients with end-stage lung, liver and heart diseases. The development of immunosuppressive agents including calcineurin inhibitors and induction therapy with antibodies has markedly decreased the incidence of acute rejection. However, long-term graft survival has not correspondingly improved. Since the strongest predictor of chronic rejection was the occurrence of acute rejection, the lack of improvement in long-term graft survival was unexpected. Thus, improvements in outcomes in clinical transplantation will require novel therapeutic strategies. One approach is the development of clinical tolerance, which is the focus of this edition and remains the “holy grail” in transplantation research. The definition of tolerance is commonly considered to be the lack of rejection in the absence of immunosuppressive treatment. However, based on mechanistic studies in model systems, it is apparent that tolerance is complex and involves multiple mechanisms. Furthermore, the incidence of graft rejection varies markedly among different organs. For example, lung transplant recipients have the worst outcomes of all solid organ recipients, whereas approximately 20% of all liver transplant recipients can be successfully weaned from immunosuppressive drugs. Based on these considerations, this edition will include reviews that discuss clinical tolerance in kidney, lung and liver transplantation. In addition, reviews of the various immune components and cellular subsets that contribute to the rejection process are included. …