New approaches in tolerance induction

Induction of transplantation tolerance permitting stable engraftment of allografts without life-long immunosuppression has gained tremendous momentum. There is compelling evidence that acquisition of tolerance is an active and highly regulated process that requires active engagement of alloantigens by the host immune system. Thus, current immunosuppressive protocols that nonselectively repress host immune activation and create a state of generalized immunosuppression are incompatible with tolerance induction. In fact, such protocols may represent a great hurdle to the induction of permanent engraftment in the clinic. A detailed understanding of the unique aspects of T-cell activation, such as T-cell costimulation, T-cell growth factors, and the underlying mechanisms involved in tolerance induction, may prove to be critically important in designing new therapeutic strategies used to induce transplantation tolerance.