Regulation of lymphocyte traffic to mucosa-associated lymphatic tissues.

Lymphocyte recognition and binding to endothelial cells at sites where lymphocytes exit the blood is controlled by several molecules. At mucosal sites, the lymphocytes use at least VLA-4, CD44, and LFA-1 (CD18/CD11a) to bind the endothelial cell ligand molecules. The endothelial cell surface ligand for CD44 is probably a human equivalent of MECA-367 and hyaluronate. LFA-1 can bind to ICAM-1/ICAM-2; and VLA-4, to VCAM-1 on endothelium. However, for physiologic lymphocyte migration, these molecules may still need additional ligands that are currently uncharacterized. At sites of inflammation, cytokines increase the expression of ICAM-1, VCAM-1, and a third endothelial cell antigen, ELAM-1, whose counter-receptor on leukocyte surface is presently unknown. Upregulation of these molecules apparently facilitates the traffic of lymphocytes and other leukocytes to sites of inflammation, thus partially determining the nature and extent of inflammation. These same molecules may be equally responsible for the pathologic characteristics of the immune response seen, for example, in inflammatory bowel diseases.