Solid Organ Transplantation: Rejection, Immunosuppression, and Tolerance

Solid organ transplantation is a lifesaving technique for end-organ failure. However, the human immune system creates considerable challenges for both early and late graft survival. The vast majority of patients require lifelong treatment with immunosuppressive medications to prevent rejection, and it is the rare patient that has donor-specific hyporesponsiveness or tolerance. Both warm and cold ischemia at the time of organ acquisition trigger an innate immune response, which in turn activates the adaptive immune system capable of responding to both major and minor histocompatibility antigens mismatched between the organ donor and the recipient. Long-term survival is affected by both immune and nonimmune injuries. Advances in immunosuppressive strategies have improved early graft survival and reduced rates of cellular rejection. Critical challenges are a sufficient supply of donor organs and antibody-mediated injury where effective therapies are lacking.