Recent advances in the immunology of chronic rejection

Chronic allograft rejection is a slowly progressive, insidious process in which the host immune system continues to mount an immunological attack on a transplanted organ, ultimately resulting in the failure of the graft. To varying degrees, all solid organ grafts are at risk for chronic rejection and undergo a stereotypic process of injury and inflammation, eventually leading to parenchymal fibrosis. The clinical consequences of chronic rejection are particularly apparent in thoracic transplantation, where both patient and graft survival decline steadily over time and the opportunities for re-transplantation or long-term extracorporeal support are limited. A variety of antigen-dependent and antigen-independent factors are known to modulate the propensity for an organ to undergo chronic rejection. Recent clinical and laboratory research has suggested that distinct immunologic mechanisms may underlie the process of chronic rejection. Ultimately, strategies to induce long-term tolerance to alloantigens will be necessary to prevent chronic rejection and to abrogate the deleterious sequelae of chronic immunosuppression.