Thymic vasculature: organizer of the medullary epithelial compartment?

The epithelial component of the thymic environment is organized into discre te cortical and medullary compartments that mediate different aspects of th ymocyte differentiation. The processes controlling the growth and organizat ion of these epithelial compartments are poorly defined. In this study we h ave used a novel approach to define the three-dimensional organization of t hymic epithelial (TE) compartments to demonstrate that the organization of the medullary TE compartment is very complex. A spatial relationship of med ullary thymic epithelium with vascular elements of the thymus was demonstra ted by simultaneous immunohistochemical labeling of vascular elements and m edullary TE. Medullary TE was often arranged as perivascular cuffs surround ing intermediate-sized vessels, but was not associated with either the capi llary network or large centrally located vessels. Similar analyses of RAG-2 (-/-) thymi revealed a striking physical association of medullary TE with v ascular elements. Ultrastructural analysis of the RAG-2(-/-) thymus indicat ed a preferential association of focal accumulations of medullary TE with p ostcapillary venules. These data suggest that discrete segments of the thym ic vasculature provide cues that act in concert with thymocyte-derived stim uli to effect normal development of the thymic environment.