Trafficking from the bone marrow to the thymus: A prerequisite for T lymphopoiesis

T cell development in the thymus throughout adult life requires the input of hematopoietic progenitors from the bone marrow via the blood. However, the ability of variously progenitors with T lineage potential to reach the thymus under physiological conditions has not been previously evaluated. In this work, I have assessed two steps required for progenitors to reach the thymus: mobilization from bone marrow to blood and settling from blood to the thymus. I found that hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs) were both present in blood, indicating that they have physiological access to the thymus, whereas downstream common lymphoid progenitors (CLPs) could not be identified in blood above the limit of detection. However, when placed in the blood of unirradiated recipients, HSCs where unable to settle within the thymus, whereas MPPs and CLPs both rapidly generated T lineage progeny within the thymus. I conclude that both mobilization and thymus settling are selective processes. I further conclude that MPPs are the principal progenitors to migrate from the bone marrow to the thymus in order to generate T cells throughout adult life