Clinical transplantation tolerance: the promise and challenges

Organ transplantation is now well established as a preferred option for the treatment of end-stage organ failure. However, there is a severe shortage of donor organs and continued loss of a significant number of organ grafts due to chronic allograft dysfunction. Induction of tolerance of a transplant recipient toward their foreign organ graft, therefore, remains the "Holy Grail" of transplantation immunobiologists. Recently, clinical trials to explore pilot tolerance protocols in humans have been initiated. Defining the ideal strategy(ies) and the role of immunosuppressive drugs, developing tolerance assay(s), and enhancing cooperation between transplant professionals, industry, and the government are some of the challenges to achieving clinical transplantation tolerance. This article reviews the promise and the challenges of achieving clinical transplantation tolerance in human organ transplant recipients.