Tolerance and its clinical significance

Several aspects of fetally or neonatally induced tolerance are briefly cons idered, and a variety of strategies for the induction of specific tolerance in adult animals or patients are discussed. They include the following: (1 ) augmentation of organ transplantation with donor-specific hone marrow; (2 ) the "prope" tolerance postulated by R.Y. Calne following treatment of kid ney transplant recipients with a powerful monoclonal antibody; (3) linked e pitope suppression, a form of specific tolerance for fully allogeneic haplo types that ran be induced in adult animals with a single major histocompati bility: complex (MHC) epitope provided it is presented on the same antigen- presenting cells as the other MHC antigens; (4) allogeneic mixed chimerism, induced in experimental animals by the inoculation of allogeneic bone marr ow into adult animals that had been subjected to a nonmyelusuppressive regi men, avoiding whole body irradiation; (5) several other approaches, viz., t otal lymphoid irradiation with bone marrow infusion, intrathymically induce d tolerance, and the still rather mysterious case of the maternally noninhe rited HLA antigens of siblings. All or some of these strategies may yet com e into their own in clinical transplantation, as the induction of specific tolerance must still be regarded as the most satisfactory solution to the p roblems of allogeneic, and perhaps xenogeneic, transplantation.