Routes to allograft survival

The field of allogeneic transplantation continues in search of its holy grail — indefinite allograft survival and true alloantigen-specific tolerance without the need for chronic immunosuppression. That this goal has remained elusive reflects our fundamental uncertainty regarding the active and passive immunologic mechanisms that define the tolerant state. Diverse methods including costimulatory blockade, T-cell depletion, micro- and macrochimerism, and the induction of active, persistent regulatory mechanisms all improve allograft survival, but it is not known whether they lead to several distinct types of tolerance or whether they activate a single common pathway required for tolerance.