Specific Immunosuppression by Local Lymphoid Irradiation Using Subcutaneous Injection of Palladium-109 Labeled Allogeneic Lymphocytes

Abstract

We have previously shown that intravenously administered palladium-109 labeled lymphocytes (Pd-L) migrated specifically to peripheral lymphoid organs where they caused selective lymphoid irradiation resulting in significantly prolonged cardiac allograft survival. This study evaluates the biodistribution of subcutaneously injected allogeneic Pd-L and the capacity of such labeled cells carrying a large dose of irradiation at a local site to attract and subsequently delete alloreactive T lymphocytes. It was hypothesized that subcutaneously administered allogeneic lymphocytes labeled with a large dose of palladium-109 will attract and then kill by irradiation the host effector cells which might permit prolongation of donor-specific allograft via partial clonal deletion. The results showed that 80% (injected dose) of subcutaneously injected allogeneic Pd-L remained at the site of administration while 20% of injected dose/gram was localized in the ipsilateral popliteal lymph node. No significant radioactivity was found in the other lymphoid and nonlymphoid organs. Pd-L effectively deleted the donor-specific effector cells, as measured by specific unresponsiveness to donor lymphocytes in mixed lymphocyte reaction. Donor cardiac allograft survival, however, was not prolonged over that found in naive recipient controls, although it was significantly prolonged when compared to cardiac allograft survival in controls sensitized by identical injections of unmodified subcutaneous allogeneic lymphocytes (mean survival time +/- SD of 6.5 +/- 0.8 vs. 3.0 +/- 0.6 days). These results suggest that partial clonal deletion of specific alloreactive cells achieved by this approach alone is insufficient to induce unresponsiveness to allografts in vivo.