The Lymphopoiesis Unit identified within the first cells that seed the thymus a unique population of lymphoid progenitors. These cells can generate lymphoid tissue inducer or invariant T cells, two cell types that are critical in the immune system. They are required to ensure thymic medullary epithelial cell maturation and negative selection, at birth. These results highlight the relevance of a sequential thymic colonization by distinct precursors for thymus organogenesis.
In this study, two distinct waves of thymic seeding progenitors, differentially regulated in time and space have been identified, during embryonic development. The origin, differentiation potential and function of the first wave of thymic seeding progenitors were, however, unclear.
In their paper, the authors showed that the first thymic seeding progenitors do not significantly contribute to the T cell repertoire of conventional T cells. Instead, they comprise a unique population of bipotent cells that generate thymic lymphoid tissue inducer and invariant T cells, only found between E12-E14 of gestation. Temporal depletion of early thymic progenitors showed that, consistent with previous observations, their progeny is indispensable for the differentiation of autoimmune regulator expressing medullary thymic epithelial cells, at birth, required for the negative selection of conventional T cells.
The first wave of thymic seeding progenitors is not of yolk sac origin but coincides in time with the first multipotent progenitors generated in the dorsal aorta, despite the overlap between lymphopoiesis initiation and transient expression of lymphoid associated transcripts in the yolk sac erythromyeloid restricted precursors. This transient expression of lymphoid associated transcripts is found in the erythromyeloid progenitors shortly after emerging in the vasculature of the yolk sac, does not impact their differentiation potential as they cannot generate lymphoid cells and is restricted to fetal hematopoiesis.
This work highlights the relevance of the developmental timing on the emergence of lymphoid subsets, all of which are required through different mechanisms for the establishment of a diverse immune system.