Current status and prospect of T cell costimulatory blockade in transplantation

Organ transplantation has been widely accepted as a routine medical treatment in Japan. The recent introduction of new immunosuppressive reagents may improve outcome after transplantation. However, further investigations are required to achieve the prevention of chronic rejection and the induction of donor-specific tolerance in clinical transplantation. The potential of costimulatory blockade in controlling allograft rejection is now extensively under investigation. Although costimulatory blockade can prevent rejection and induce tolerance experimentally, there are several issues that need to be clarified before its clinical application. Recently, several novel costimulatory pathways have also been reported. Each costimulatory pathway has distinct and unique immunological roles in T cell activation and down-regulation. Upon the perception of underlying mechanisms, the theoretical and effective use of costimulatory blockade in combination with conventional immunosuppression and/or novel molecular targeting therapies might make a major breakthrough in clinical transplantation.