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What is an HEV?

Lymphocytes enter lymph nodes directly from the blood by migrating across the walls of specialized postcapillary venules which are located in the paracortex (T lymphocyte areas) of the node. These vessels have a characteristic morphology which distinguishes them from other types of blood vessel. The endothelial cells which line these vessels have a plump or cuboidal morphology, which contrasts to the flattened morphology of endothelial cells lining other types of vessel (Figure 1). It is the peculiar endothelial morphology that has engendered their common name – high endothelial venules (HEVs). The endothelial lining is surrounded by a thickened basement membrane, which is more pronounced than in other types of blood vessel. In immunocompetent adults, the localization of lymphocytes, but not other leukocytes, either attached to the inner (luminal) surface or within the vessel wall and the distinct morphological appearance are the most recognizable features of HEV. However, these vessels are also readily distinguishable from other blood vessels by histochemical, biochemical and immunological markers. The lining endothelial cells, which will be referred to as high endothelial cells (HECs), stain more intensely with RNA-binding dyes such as pyronin and contain a prominent Golgi apparatus and more secretory vesicles than other types of endothelia. Early histochemical studies also distinguished HEC from ‘flat’ endothelial cells lining other types of vessel. HEC express higher levels of nonspecific esterase, lactate dehydrogenase and NADH reductase. Biochemical studies identified a unique biosynthetic pathway for inorganic sulfate in HECs which is crucial for the generation of the peripheral addressin, an important adhesion molecule which mediates l-selectin-dependent binding of lymphocytes to HECs (see below). Several monoclonal antibodies have been described that specifically stain HEVs and not other types of blood vessel. These include MECA 79 and MECA 367, which identify the peripheral and mucosal addressins respectively, HECA 452, which identifies part of the functional carbohydrate epitope in the peripheral addressin, the sialyl Lewis^x saccharide and MECA 325, for which the antigen has not yet been identified.