SELECTIVE DIFFERENCES IN VASCULAR ENDOTHELIAL VS AIRWAY EPITHELIAL T-CELL ADHESION MECHANISMS

The basis for T cell adhesion to airway epithelial and vascular endoth elial cells was studied using a quantitative flow cytometry-based assa y that avoids extensive leukocyte purification and labeling. Compared with standard cell-labeling methods, the flow cytometry-based assay yi elded a lower level of constitutive T cell adhesion, despite a similar level of stimulated adhesion (after T cell activation with phorbol di butyrate) using endothelial or epithelial cell monolayers. Endothelial T cell adhesion was further increased by monolayer treatment with tum or necrosis factor-alpha (less so with interleukin-lp and least with i nterferon-gamma), whereas epithelial T cell adhesion was most sensitiv e to interferon-gamma. Cytokine stimulation of adhesion was invariably concentration dependent and closely matched to the cellular levels of intracellular adhesion molecule-1 (ICAM-1). Accordingly, stimulated T cell adhesion was markedly inhibited by anti-ICAM-1 or anti-beta(2)-i ntegrin antibody (95-97% inhibition for epithelial cells and 57-67% in hibition for endothelial cells) directed against ICAM-1 interaction wi th lymphocyte function-associated antigen-1 (LFA-1; alpha(L) beta(2)-i ntegrin). Residual endothelial T cell adhesion that correlated with en dothelial vascular cell adhesion molecule-1 (VCAM-1) levels was blocke d by an anti-alpha(4)-integrin antibody directed against VCAM-1 intera ction with very late activation antigen-4 (VLA-4; alpha(4) beta(1)-int egrin). The results suggest that 1) peripheral blood T cells without e xogenous activation exhibit little LFA-1- or VLA-4-dependent adherence except to endothelial or epithelial cells expressing high levels of I CAM-1 and/or VCAM-1; and 2) differences in endothelial vs. epithelial cell mechanisms to bind activated and unactivated T cells (e.g., depen dence on a mixed- vs. a single-ligand system and distinct cytokine-res ponsiveness of ligand levels) may help to coordinate T cell traffic to epithelial barriers.