The pursuit of transplantation tolerance: new mechanistic insights

Donor-specific transplantation tolerance that enables weaning from immunosuppressive drugs but retains immune competence to non-graft antigens has been a lasting pursuit since the discovery of neonatal tolerance. More recently, efforts have been devoted not only to understanding how transplantation tolerance can be induced but also the mechanisms necessary to maintain it as well as how inflammatory exposure challenges its durability. This review focuses on recent advances regarding key peripheral mechanisms of T cell tolerance, with the underlying hypothesis that a combination of several of these mechanisms may afford a more robust and durable tolerance and that a better understanding of these individual pathways may permit longitudinal tracking of tolerance following clinical transplantation to serve as biomarkers. This review may enable a personalized assessment of the degree of tolerance in individual patients and the opportunity to strengthen the robustness of peripheral tolerance