Tolerance and chronic rejection

The most common cause of chronic allograft loss is an incompletely understo od clinicopathological entity called chronic rejection (CR). Recent reports suggest an improvement in long-term renal allograft survival, although it is not clear from these data whether a true reduction of biopsy-proven CR h as occurred. Although newer immunosupressive medications have e greatly red uced tile incidence of acute rejection (AR) in the early post-transplantati on period the ideal therapy for both AR and CR would be to achieve a state of tolerance. By definition, such a state should allow for indefinite allog raft survival, with no histopathological evidence of CR, despite immunocomp etence in the host (i.e. without the need for chronic immunosupression). Al though several experimental studies are able to achieve tolerance, with cle ar improvement in allograft survival, detailed studies on graft function an d morphology are often not included. This review will discuss possible ways that tolerance induction could lead to a CR-free state. General mechanisms of CR and transplantation tolerance induction are discussed as well as the difficulties in translating small animals studies into large animals and h umans.