SELECTIVE LYMPHOID IRRADIATION

Abstract

Palladium-109-hematoporphyrin (Pd-H) is a β-emitting radioisotope with a wide safety margin between the effective and lethal doses. A single systemic injection of Pd-H localizes preferentially in the lymphoid organs and produces lymphatic and central bone marrow ablation while sparing the distal bone marrow and gastrointestinal mucosa. Selective lymphoid irradiation with Pd-H alone at one-half of the LD50 dose is not sufficient to prolong rat cardiac allograft survival without additional minimal pretreatment with antilymphocyte globulin (ALG). A sublethal dose of Pd-H (30 me/kg) with two doses of ALG (10 mg) as pretransplant treatment of Lewis recipients led to a permanent and specific acceptance of Fischer heart allografts (>450 days) and significant prolongation of ACI heart allografts. Long-term Lewis recipients of Fischer heart allografts (>150 days) demonstrated specific unresponsiveness to donor tissue by accepting a second Fischer heart allograft permanently while rejecting a third-party (ACI) heart. Lewis rats were pretreated with sublethal total-body irradiation (TBI) with and without 20 mg of ALG and received Fischer or ACI cardiac allografts. The mortality in these groups after operation was 40% (TBI alone) and 83% (TBI and ALG). Cardiac allograft survival was similar to that found in groups pretreated with Pd-H and ALG. It is concluded that selective lymphoid irradiation administered systemically is an effective, safe, and quick method of host pretreatment for prolonged allograft acceptance and may be potentially useful in induction of immunological tolerance.