Kidney Allograft Survival in Dogs Treated with Total Lymphoid Irradiation

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Abstract
Total lymphoid irradiation (TLI) is immunosuppressive and, in rodents, can induce a state where transplantation of allogeneic bone marrow results in chimerism and permanent acceptance of organ allografts from the donor strain. We attempted to apply this treatment to a large animal model. Twelve splenectomized dogs were treated with TLI (150 rads per fraction, total dose 1950–3000 rads) before bilateral nephrectomy and renal allotransplantation. Eight dogs received bone marrow from the kidney donor. In 13 untreated control dogs renal allografts functioned (serum creatinine level < 2.0 mg/dl) for a mean (SE) of 4.7 ± 0.3 days. In the four TLI treated dogs who did not receive bone marrow the renal allografts functioned for 15–76 days (two dogs died with functioning grafts). In the eight TLI treated dogs who received donor bone marrow, two died immediately after transplantation, two rejected at 3 and 13 days, one died at 13 days with a functioning graft, and two have had the grafts function for longer than 500 days. Chimerism was not detected in the one dog tested. The response of peripheral blood lymphocytes to stimulation with phytohemaglutinin and in mixed lymphocyte culture was suppressed for at least one month after TLI. The results confirm the immunosuppressive effect of TLI. The absence of kidney rejection in two recipients of donor bone marrow show the potential of this approach to induce long-term immunologic unresponsiveness as to an organ allograft, but the outcome is unpredictable and further experiments are needed to define the optimal conditions for administration of TLI and bone marrow to the recipients.