High endothelial venules

High endothelial venules (HEV) are specialized post-capillary venules characterized by plump endothelial cells as opposed to the usual flatter endothelial cells found in regular venules.^[1] HEVs enable lymphocytes circulating in the blood to directly enter a lymph node (by crossing through the HEV).^[2][3]

In humans, HEVs are found in all secondary lymphoid organs (with the exception of spleen, where blood exits through open arterioles and enters the red pulp), including hundreds of lymph nodes dispersed in the body, tonsils and adenoids in the pharynx, Peyer's patches (PIs) in the small intestine, appendix, and small aggregates of lymphoid tissue in the stomach and large intestine.^[4] In contrast to the endothelial cells from other vessels, the high endothelial cells of HEVs have a distinctive appearance, consisting of a cuboidal morphology and with various receptors to interact with leukocytes (express specialized ligands for lymphocytes and are able to support high levels of lymphocyte extravasation).^[4] HEVs enable naïve lymphocytes to move in and out of the lymph nodes from the circulatory system. HEV cells express addressins, which are specific adhesion molecules that attach to the L-selectins on lymphocytes and anchor them to the HEV wall in preparation for crossing the endothelium.

The endothelial cells of HEVs have a 'plump' appearance different from the flat morphology of endothelial cells that line other vessels, and are therefore called high endothelial cells by reference to their thickness.^[4] Another characteristic of HEVs, revealed by light-microscopic examination, is the presence of a large number of lymphocytes within their walls. This illustrates the function of HEVs in lymphocyte recruitment and explains why these vessels were implicated in lymphocyte traffic from the time of their initial description.