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Mechanisms of Graft Rejection and Acceptance: Pathways to a New Clinical Era
Identification of Operational Tolerance in Clinical Liver Transplantation
Alberto Sanchez-Fueyo, Hospital Clinic Barcelona, Barcelona, Spain
Liver transplant recipients can occasionally discontinue all immunosuppressive therapies without undergoing rejection. However, accurate identification of operationally tolerant recipients remains a challenge. To design a clinically applicable molecular test of tolerance in liver transplantation and to understand the molecular and cellular basis of tolerance in liver transplantation, we studied transcriptional patterns from tolerant and non-tolerant liver transplant recipients. This resulted in the discovery and validation of several gene signatures comprising a modest number of genes capable of identifying tolerant and non-tolerant recipients with high accuracy. The expression program of NK cells and γδT cells exert a predominant influence over the tolerance-related transcriptional patterns suggesting that they may be critical in the maintenance of liver allograft tolerance. We conclude that transcriptional profiling of peripheral blood can be employed to identify liver transplant recipients who can discontinue immunosuppressive therapy and that innate immune cells are likely to play a major role in the maintenance of operational tolerance in liver transplantation.