Tolerance and its clinical significance.

Several aspects of fetally or neonatally induced tolerance are briefly considered, 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 bone marrow; (2) the "prope" tolerance postulated by R.Y. Calne following treatment of kidney transplant recipients with a powerful monoclonal antibody; (3) linked epitope suppression, a form of specific tolerance for fully allogeneic haplotypes that can be induced in adult animals with a single major histocompatibility 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 marrow into adult animals that had been subjected to a nonmyelosuppressive regimen, avoiding whole body irradiation; (5) several other approaches, viz., total lymphoid irradiation with bone marrow infusion, intrathymically induced tolerance, and the still rather mysterious case of the maternally noninherited HLA antigens of siblings. All or some of these strategies may yet come into their own in clinical transplantation, as the induction of specific tolerance must still be regarded as the most satisfactory solution to the problems of allogeneic, and perhaps xenogeneic, transplantation.