Selective lymphoid irradiation. VI. Effect of palladium-109-labeled lymphocytes on rat cardiac allograft survival.

ABSTRACT

We have previously shown that pretransplant treatment with palladium-109 hematoporphyrin (Pd-H) and two small doses of antilymphocyte globulin (ALG) leads to donor-specific permanent acceptance of cardiac allografts in weakly histoincompatible rat combinations and significant prolongation of hearts in the ACI-to-Lewis strains. Pd-H also concentrates in nonlymphoid organs to a significant degree that is undesirable, so we have examined, in the present study, the efficacy of Pd-109 attached to lymphocytes in producing selective lymphoid irradiation and compared it with the immunosuppressive effect of Pd-H. Adoptive transfer of syngeneic lymphocytes labeled with palladium-109 (Pd-L) led to significant concentration of radioactivity in the peripheral lymphoid organs relative to the bone marrow (BM), intestine, thymus, and endocrine organs. The concentration of radioactivity in the spleen relative to BM and intestinal mucosa was 231 and 581, respectively. The immunosuppressive efficacy of a suboptimal dose of 3 mCi (one-third of the dose used in our earlier reports with Pd-H) administered via Pd-L (6 X 10(9) cells) at 4 days combined with 5 mg ALG at 2 days and 1 day prior to transplantation was compared in its effect on cardiac allografts with a similar dose of Pd-H (3 mCi) combined with ALG. The mean survival time (MST) of 6.5 +/- 0.4 days in untreated recipients was moderately prolonged to 14.6 +/- 3.0 days by Pd-H and ALG, and was not significantly different from an MST of 14.1 +/- 0.3 days achieved with 2 doses of ALG alone. Pretransplant treatment of Lewis rats with Pd-L and ALG produced a significant prolongation of ACI heart allografts to 30.5 +/- 3.1 days (P less than 0.001). These results suggest that Pd-L is more effective in prolonging rat cardiac allografts than a similar dose of Pd-H, and thus it may be a new method of selective lymphoid irradiation prior to transplantation.