Current status of allograft tolerance in intestinal transplantation

Solid organ transplantation has become a clinical practice after the development of different immunosuppressive drugs that allowed controlling rejection. The price to be paid for that is the permanent risk of infections and malignancies and a significant drug-associated toxicity. The establishment of transplant tolerance has been the "holy grail" for transplantation medicine since its beginnings. Different experimental approaches and clinical trials resulted in the accumulation of knowledge on mechanisms and strategies that favor the establishment of tolerance without achieving the objective of autonomous allograft tolerance in the clinical field. Development of tolerance in intestinal transplantation constitutes a challenging situation due to several particular features that contribute to the generation of a strong allogeneic response. In the present review, we summarize the different immune mechanisms that may contribute to allograft tolerance. The different barriers that should be bypassed in intestinal transplantation to tolerate the graft are discussed. Finally, we revise the strategies that were applied with different degrees of success in the clinical field including the most promising recent approaches and the forthcoming candidates in the field that might be translated into clinical trials in the near future.