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Transplantation tolerance after allograft rejection

Purpose of review Although elusive for many decades, transplantation tolerance can now be achieved in the clinic. This has prompted follow-up investigations into its stability and longevity, as well as into barriers to its induction, which include memory T and B cells. Recent findings Clinical observations reveal that transplantation tolerance can be induced in adult recipients and that even episodes of acute rejection do not preclude successful weaning from immunosuppression to reveal tolerance. These observations appear to conflict with the currently accepted notion that adult transplant recipients harbor high frequencies of memory human leukocyte antigen-specific T cells that are a barrier to transplantation tolerance. We discuss how these observations may be rationalized, by proposing the generation of helpless effector CD8+ T cells that cannot develop into memory, and by highlighting recent findings on the ability of transplantation tolerance to be spontaneously restored after rejection. We speculate that in individuals who develop tolerance while on immunosuppression and then experience rejection, it is this restored tolerance that is revealed upon successful weaning of immunosuppression. Summary We have reviewed clinical and experimental data to explain how transplantation tolerance may be achieved in individuals who have experienced allograft rejection.