A Lymphocyte Homing Receptor: A Member of an Emerging Class of Cell Adhesion Molecules

The body contains a collection of scattered lymphoid organs, which drain all potential portals of entry for foreign substances. Antigens that enter through the skin are carried by the lymph to cutaneous lymphnodes; antigens that enter through the gut are collected by gut-associated lymphoid organs such as Peyer’s patches, and antigens in the blood are filtered out by the spleen. Any particular antigen can activate only a small percentage of the immunocompetent lymphocytes. To maximize the probability that this small number of cells comes into contact with a cognate antigen that becomes localized in a particular lymphoid organ, there is a continuous and massive recirculation of lymphocytes between the blood and all the lymphoid organs (see review by Yednock and Rosen 1989). In this way the body’s repertoire of immunocompetent B- and T-cells are eventually brought into contact with the antigen, in whichever of the widely scattered lymphoid organs the antigen has become sequestered. Lymphocytes move from one lymphoid organ to the next by alternatively traveling via the blood and the lymph. In murine, human and other mammalian species, the portal of entry of blood-borne lymphocytes into secondary lymphoid organs (except the spleen) is through high endothelial venules or HEV. These are postcapillary venules characterized by tall or cuboidal endothelial lining cells. Lymphocytes adhere to these specialized endothelial cells and subsequently migrate into the parenchyma of the lymphoid organ. Since the HEV was first recognized as the primary site of lymphocyte emigration from the blood into secondary lymphoid organs (Gowans and Knight 1964)., there has been great interest in the nature of the adhesive interaction between the lymphocytes and the endothelial cells of the HEV.