Induction of donor-specific tolerance to heart transplantation: From concept to clinical translation

While significant progress has been made in the 54 years since the world's first heart transplant in 1967, the longevity of heart transplants is limited by rejection and the innumerable complications of chronic immunosupadministered ideally, have evolved to offer reliable protection against most acute forms of rejection, they remain imperfect because of their lack of donor specificity, opportunistic infections, and significant medication toxicities. Instead, one of the goals that the field has been working toward is tolerance. Operational donor-specific tolerance requires 2 key features: The recipient does not reject the graft despite the absence of sustained immunomodulatory treatment and still retains the ability to mount adequate protective and regulatory immune responses. Tolerance has been considered the Holy Grail, because it would effectively eliminate the need for chronic immunosuppression and improve heart transplant longevity. Like the Grail, its existence is suspect, but the quest for it remains laudable. This review seeks to discuss the methods for inducing donor-specific tolerance in heart transplantation and their clinical potential.