In this issue of Blood, Zlotoff and colleagues demonstrate that despite relaxed entry requirements after irradiation and hematopoietic stem cell transplantation (HSCT), insufficient supply of bone marrow (BM) T-cell progenitors acts as a limiting factor to thymic reconstitution, contributing toward delayed T-cell recovery.The thymus contains no self-renewing T-cell progenitors, but instead relies on the importation of BM-derived precursors from the circulation. The identity of this blood-borne progenitor, and in particular the extent of its lineage commitment, remains elusive and even controversial. However, mounting evidence suggests that there may actually be multiple progenitors with T lineage and thymic seeding capacity, which all contribute to thymopoiesis. Interestingly, while the precise identity of the thymus-seeding T-cell progenitor remains contentious, the mechanism by which these cells gain entry to the thymus and differentiate into mature T cells has been surprisingly consistent (see figure)
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