Several approaches successfully achieve allograft tolerance in preclinical models but are
challenging to translate into clinical practice. Many clinically relevant factors can attenuate
allograft tolerance induction, including intrinsic genetic resistance, peritransplant infection,
inflammation, and preexisting antidonor immunity. The prevailing view for immune memory
as a tolerance barrier is that the host harbors memory cells that spontaneously cross-react to
donor MHC antigens. Such preexisting “heterologous” memory cells have direct reactivity to …