THE THYMIC WAY TO TRANSPLANTATION TOLERANCE

Within the past three decades, extensive research has been carried out with the aim to prevent graft rejection by minimizing the side effect s related to the use of immunosuppressants. The major goal in transpla ntation research remains the development of strategies that would allo w one to achieve a state of donor-specific unresponsiveness in order t o promote a condition of true tolerance without the need of immune-sup pressants, Recent evidence has been provided that this is a pursuing g oal, at least in experimental animals, The thymus plays the major role in the development of self-tolerance, and initial work in the late 19 60s indicated that the thymus also plays a critical role in the induct ion of acquired tolerance to exogenous antigens. Recently, the interes t in acquired thymic tolerance has been renewed by the observation tha t, in the rat, the thymus is an immunologically privileged site in whi ch isolated pancreatic islets can be engrafted and survive indefinitel y, Moreover, intrathymic injection of the islets induced donor-specifi c unresponsiveness, which allowed survival of a second donor-strain is let cell allograft transplanted into an extrathymic site, These findin gs on cellular allografts have been extended to vascularized organ all ografts, Studies have documented that, in rodents, the intrathymic inj ection of donor cells induces a state of tolerance and prolongs the su rvival of allografts, including kidney, heart, liver, and small bowel. Unresponsiveness to organ graft is donor but not tissue specific, and evidence is presented here that the thymus has a central role in such a phenomenon, The nature of the alloantigen(s) being recognized in th e thymus and the possible mechanism(s) of acquired thymic tolerance ar e reviewed.