HISTORY OF HIGH ENDOTHELIAL VENULE-LIKE VESSELS IN RHEUMATOID ARTHRITIS AND OTHER HUMAN CHRONIC INFLAMMATORY DISEASES

High endothelial venules (HEVs) are anatomically distinct postcapillary venules found in lymphoid organs. They support high levels of lymphocyte extravasation fromthe blood (1–3). The precise relationship between the structure and function of these specialized blood vessels has intrigued and fascinated many investigators over the past 100 years. The peculiar structure of HEVs in lymph nodes from Macacus cynomolgus was first observed by Thome in 1898 (4). He described these vessels as being composed of plump, cuboidal endothelial cells (ECs) whose surface strongly bulges into the vascular lumen. These ECs looked like columnar epithelial cells and Thome wrote that, at first notice, one is more inclined to think of the duct of a gland rather than that of a blood vessel. It is this cuboidal or columnar appearance that has given rise to the names high ECs and high endothelial venules. The observations of Thome were confirmed in other species, including human, by von Schumacher, who was the first to note the presence of numerous lymphocytes within the wall of HEVs (5). Vessels of the HEV type, characterized by a plump endothelial lining with many adherent and infiltrating lymphocytes, were later observed in Peyer patches and tonsils. Although the occurrence of lymphocytes within HEV walls was first noted in 1899 (5), the direction and physiological significance of lymphocyte migration through HEVs was not fully appreciated until the classical autoradiographic experiments of Gowans and Knight (6).