During steady state lymphopoiesis in the postnatal thymus, migration of precursors outward from the deep cortex toward the capsule is required for normal differentiation. Such migration requires, at a minimum, expression of adhesive receptors on the migrating lymphoid cells, as well as a stable matrix of their ligands persisting throughout the region of migration. In this study, we address the nature of this adhesive matrix. Although some precursor stages bound efficiently to extracellular matrix ligands, a specific requirement for the cell surface ligand VCAM-1 was also found. In situ analysis revealed that early precursors are found in intimate contact with a matrix formed by stromal cells in the cortex, a proportion of which expresses VCAM-1. In vivo administration of an anti-VCAM-1 Ab resulted in decreased thymic size and altered distribution of early precursors within the cortex. These results indicate that precursors migrating outward through the cortex may use a cellular, rather than extracellular, matrix for adhesion, and suggest that the VCAM-1+ subset of cortical stroma may play a crucial role in supporting the migration of early precursors in the steady state thymus.

T cell progenitors derive from the bone marrow but must migrate via bloodstream to the thymus in order to differentiate. The mechanism by which the thymus recruits progenitors from the blood is unknown. It is known, however, that there are receptive and refractory periods for progenitor recruitment and that when cells are imported, they enter the thymus through post-capillary venules. Therefore, recruitment is an active process temporally and spatially regulated. In order to characterize the mechanism of recruitment, we evaluated vascular signals known to regulate leukocyte extravasation, with respect to their intrathymic location and temporal fluctuations. We find that CD34, MECA79, VCAM-1, ICAM-1 and VAP-1 are all expressed in thymic blood vessels. MECA79 and VAP-1 appear to be specific for post-capillary venules, while ICAM-1 and VCAM-1 are also found on intrathymic stromal cells. MAdCAM is also expressed in the thymus, but is not associated with vascular tissues. Only MECA79 is upregulated during recruitment peaks, suggesting a role for this molecule in the periodicity of recruitment. Together, these studies reveal potential roles for L-selectin ligands, VCAM-1, ICAM-1 and VAP-1 in progenitor recruitment to the thymus, and implicate the presence of other periodic signals, such as chemokines and cytokines, that cooperate to execute this essential function.