VASCULAR CELL-ADHESION MOLECULE-1 IS EXPRESSED BY CORTICAL THYMIC EPITHELIAL-CELLS AND MEDIATES THYMOCYTE ADHESION - IMPLICATIONS FOR THE FUNCTION OF ALPHA-4-BETA-1 (VLA4) INTEGRIN IN T-CELL DEVELOPMENT

T-cell development requires a series of discrete selection and activat ion signals delivered to maturing progenitors in the thymic cortex and medulla. We have previously shown the constitutive activity of the in tegrin, alpha 4 beta 1 (VLA4), on a unique subpopulation of immature c ortical thymocytes and proposed a role for integrin-mediated adhesion in positive selection by cortical epithelium, In the present report we show that thymic epithelial cell lines express vascular cell adhesion molecule-1 (VCAM-1) a high-affinity ligand for alpha 4 beta 1, and th at VCAM-1 mediates thymocyte binding to these lines. Immunohistochemis try and confocal microscopy show that VCAM-1 is selectively expressed in situ by thymic epithelium in the cortex and corticomedullary juncti on, two locations at which VCAM-1 could determine the interaction betw een immature thymocytes and selecting elements on epithelial cells. In parallel, we confirmed that fibronectin (FN), the alternative ligand for alpha 4 beta 1, is expressed predominantly in the medulla, These r esults suggest that VCAM-1 is an adhesive ligand in the thymic cortex for the activated form of alpha 4 beta 1 constitutively expressed duri ng development by immature double positive thymocytes. The structural segregation of the alternative ligand, FN, to the medulla suggests tha t medullary FN may regulate the migration, development, and export of more mature thymocytes. (C) 1997 by The American Society of Hematology .