The basis for T cell adhesion to airway epithelial and vascular endothelial cells was studied using a quantitative flow cytometry-based assay that avoids extensive leukocyte purification and labeling. Compared with standard cell-labeling methods, the flow cytometry-based assay yielded a lower level of constitutive T cell adhesion, despite a similar level of stimulated adhesion (after T cell activation with phorbol dibutyrate) using endothelial or epithelial cell monolayers. Endothelial T cell adhesion was further increased by monolayer treatment with tumor necrosis factor-α (less so with interleukin-1β and least with interferon-γ), whereas epithelial T cell adhesion was most sensitive to interferon-γ. 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- β2-integrin antibody (95-97% inhibition for epithelial cells and 57-67% inhibition for endothelial cells) directed against ICAM-1 interaction with lymphocyte function-associated antigen-1 (LFA-1; α(L)β2-integrin). Residual endothelial T cell adhesion that correlated with endothelial vascular cell adhesion molecule-1 (VCAM-1) levels was blocked by an anti- α4-integrin antibody directed against VCAM-1 interaction with very late activation antigen-4 (VLA-4; α4β1-integrin). The results suggest that 1) peripheral blood T cells without exogenous activation exhibit little LFA-1- or VLA-4-dependent adherence except to endothelial or epithelial cells expressing high levels of ICAM-1 and/or VCAM-1; and 2) differences in endothelial vs. epithelial cell mechanisms to bind activated and unactivated T cells (e.g., dependence on a mixed- vs. a single-ligand system and distinct cytokine-responsiveness of ligand levels) may help to coordinate T cell traffic to epithelial barriers.
|Journal||American Journal of Physiology - Lung Cellular and Molecular Physiology|
|Issue number||4 11-4|
|State||Published - 1994|
- cell adhesion molecule