Homing of hematopoietic progenitors to the thymus is profoundly reduced after irradiation (111.32)

Abstract After bone marrow transplantation (BMT), T cells are among the last of the hematopoietic lineages to recover, but the reasons for this delay are poorly understood. Previous work on T lineage reconstitution after BMT assumed progenitor supply to the thymus was not limiting; therefore research focused on intrathymic defects as potentially underlying delayed T cell recovery. We have recently discovered that delivery of progenitors to the thymus is limiting for T cell reconstitution after BMT. We have developed an assay that directly measures settling of intravenously injected progenitors within the thymus. Using this short-term settling assay, we have found that irradiated mice exhibit dramatically reduced thymic settling by intravenously injected progenitors. Directed irradiation of the thymus alone also showed reduced thymic settling. We suggest that one defect in T cell reconstitution after BMT is due to defective progenitor homing to the thymus, as survival of progenitors in the post-irradiation environment appears intact.