It has been shown both experimentally by Medawar and in nature by Owen that exposure of various mammalian species to foreign antigens during fetal or neonatal life can result in permanent specific immunological tolerance to those antigens. Burnet proposed the clonal selection theory of acquire immunity, which explains the tolerance phenomena by the deletion of foreign antigen-specific lymphocytes which they are exposed to their respective antigens while the lymphocytes are in an immature state. These observations led to the hypothesis that an adult animal, modified so as to have a fetal-like immune system and subject to a foreign graft transplant, would develop permanent specific immunological tolerance to the graft. A junenile rhesus monkey model has been developed over the past three years to test the hypothesis. Breiefly the interventions are: 1) recipient bone marrow harvest, 2) T lymphocyte removal from the marrow by physical (E-rosette) and immunological (antibody plus complement) methods, 3) total body irradiation of the recipient with a myeloablative dose to eliminate all immunologically competent cells, 4) reinfusion into the recipient of the T lymphocyte-depleted marrow to salvage the recipient from the radiation, and 5) transplantation of an antigenically-mismatched heterotopic heart allograft. Each experiment includes a treated recipient paired with an appropriate control animal. The major endpoint is time to graft rejection, determined by loss of electrocardiographic activity and confirmed by histopaological examination. Other responses being followed are the time course of return of immunoloigcal function, and tests of specific immunoloigcal tolerance. Only recently have preliminary results become available.
