SIGNALING THROUGH CD50 (ICAM-3) STIMULATES T-LYMPHOCYTE BINDING TO HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS AND EXTRACELLULAR-MATRIX PROTEINSVIA AN INCREASE IN BETA-1 AND BETA-2 INTEGRIN FUNCTION

Regulated adhesion of T lymphocytes to antigen-presenting cells, endot helial cells and extracellular matrix proteins is crucial in T lymphoc yte activation and migration to the sites of injury. In this study, we show that three monoclonal antibodies (mAb) recognizing different epi topes on the CD50 (ICAM-3) molecule increase T lymphocyte adhesion to tumor necrosis factor (TNF)-stimulated human umbilical vein endothelia l cells and extracellular matrix proteins. These phenomena art mediate d by an increase in beta 1 and beta 2 integrin avidity since (a) CD50- induced adhesion to endothelial cells was abrogated by simultaneous bl ocking of beta 1- and beta 2-mediated adhesion pathways but not by int erfering with either one individually, (b) CD50 mAb increased beta 1 i ntegrin-mediated adhesion to extracellular matric proteins and to fibr onectin-derived synthetic peptides, (c) CD50 mAb enhanced T lymphocyte binding to ICAM-1 transfectants. and (d) CD50 mAb did not modify surf ace expression patterns of beta 1 or beta 2 integrins on T lymphocytes . Our data suggest that constitutively expressed CD50 (ICAM-3) can pla y a pivotal role in initiating a cascade of adhesion events which may be crucial in immune activation and in the development of inflammatory lesions.