Thymic vasculature: organizer of the medullary epithelial compartment?

The epithelial component of the thymic environment is organized into discrete cortical and medullary compartments that mediate different aspects of thymocyte differentiation. The processes controlling the growth and organization of these epithelial compartments are poorly defined. In this study we have used a novel approach to define the three-dimensional organization of thymic epithelial (TE) compartments to demonstrate that the organization of the medullary TE compartment is very complex. A spatial relationship of medullary thymic epithelium with vascular elements of the thymus was demonstrated by simultaneous immunohistochemical labeling of vascular elements and medullary TE. Medullary TE was often arranged as perivascular cuffs surrounding intermediate-sized vessels, but was not associated with either the capillary network or large centrally located vessels. Similar analyses of RAG-2(-/-) thymi revealed a striking physical association of medullary TE with vascular elements. Ultrastructural analysis of the RAG-2(-/-) thymus indicated a preferential association of focal accumulations of medullary TE with post-capillary venules. These data suggest that discrete segments of the thymic vasculature provide cues that act in concert with thymocyte-derived stimuli to effect normal development of the thymic environment.