Transplant immunology for non-immunologist

Transplantation is the treatment of choice for end-stage kidney, heart, lung, and liver disease. Short-term outcomes in solid-organ transplantation are excellent, but long-term outcomes remain suboptimal. Advances in immune suppression and human leukocyte antigen matching techniques have reduced the acute rejection rate to <10%. Chronic allograft injury remains problematic and is in part immune-mediated. This injury is orchestrated by a complex adaptive and innate immune system that has evolved to protect the organism from infection, but, in the context of transplantation, could result in allograft rejection. Such chronic injury is partially mediated by anti-human leukocyte antigen antibodies. Severe rejections have largely been avoided by the development of tissue-typing techniques and crossmatch testing, which are discussed in detail. Further advances in the understanding of T- and B-cell immunology have led to the development of new immunomodulatory therapies directed at prolonging allograft survival, including those that decrease antibody production as well as those that remove antibodies from circulation. Further application of these immunomodulatory therapies has allowed expansion of the donor pool in some cases by permitting ABO-incompatible transplantation and transplantation in patients with preformed antibodies. Although vast improvements have been made in allograft survival, patients must remain on lifetime immunosuppression. Withdrawal of immunosuppression almost always ultimately leads to allograft rejection. The ultimate dream of transplant biologists is the induction of tolerance, where immune function remains intact but the allograft is not rejected in the face of withdrawn immunosuppression. This, however, has remained a significant challenge in human studies.