New strategies for the treatment of chronic rejection

Chronic allograft rejection is a slow, progressive process characterized by interstitial fibrosis, luminal obliteration and declining organ function, eventually resulting in graft loss. While optimizing the immunosuppressive regimen has improved short-term allograft survival, chronic rejection remains a major cause of late graft loss. Although non-immunological mechanisms can contribute to chronic rejection, there is compelling evidence that major histocompatibility complex-driven processes play a dominant role in the development of the disease. While some immunosuppressive drugs currently in clinical use, such as mycophenolate mofetil and rapamycin, have favorable effects on the incidence of chronic graft failure, the most effective way to overcome chronic rejection may be to induce immunological tolerance.