High endothelial venules (HEVs? are specialized postcapillary venules found in lymphoid tissues that support high levels of lymphocyte extravasation from the blood. Here, Jean-Philippe Girard and Timothy Springer highlight the unique properties of HEV endotbelium, discuss the molecular mechanisms controlling HE V specialization and review evidence suggesting that HEVs could play an important role in the patbogenesis of chronic inflammatory diseases.

While patrolling the body in search of foreign antigen, lymphocytes continuously circulate from blood, through lymphoid and other tissues, and back through the lymphatics to the blood. This process, called lymphocyte recirculation, allows the dissemination of the immune response throughout the body, and thereby provides an effective immune surveillance for foreign Invaders and alterations in the body’s own cells’ J. The first critical step in lymphocyte migration from circulation into tissue is the adhesion of lymphocytes to vascular endothelium. In lymphoid organs, lymphocyte adherence and transendothelial migration occur at specialized postcapillary vascular sites called high endothelial venules (HEVs). Although HEVs are particularly abundant in the T-cell areas surrounding the B-cell follicles, they serve as the sites of entry both for T and B lymphocytes’. In humans, HEVs are found in all secondary lymphoid organs (with the exception of spleen, where lymphocyte emigration occurs via the blood sinusoids in the marginal zone), including hundreds of lymph nodes dispersed in the body, tonsils and adenoids in the pharynx, Peyer’s patches (PI%) in the small intestine, appendix, and small aggregates of lymphoid tissue in the stomach and large intestine. Moreover, HEV-like vessels are observed in chronically inflamed nonlymphoid tissues and are believed to support lymphocyte recruitment into these sites4. In contrast to the endothelial cells from other vessels, the high endothelial cells of HEVs have a distinctive appearance, express specialized ligands for lymphocytes and are able to support high levels of lymphocyte extravasation5y6. While many reviews have discussed the molecular mechanisms of lymphocyte homing and lymphocyte-HEV interactions2,‘-9, most have focused on lymphocytes and the lymphocyte homing receptor L-selectin, and considerably less attention has been given to the HEV side of the interaction. The purpose of this review is to highlight the specialized features of the HEV endothelium that allow lymphocyte emigration in HEVs to be so efficient, and to discuss the role of the tissue environment in the control of HEV specialization.