Selective differences in vascular endothelial- vs. airway epithelial-T cell adhesion mechanisms.
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-alpha (less so with interleukin-1 beta and least with interferon-gamma), whereas epithelial T cell adhesion was most sensitive 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-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; alpha L beta 2-integrin). Residual endothelial T cell adhesion that correlated with endothelial vascular cell adhesion molecule-1 (VCAM-1) levels was blocked by an anti-alpha 4-integrin antibody directed against VCAM-1 interaction with very late activation antigen-4 (VLA-4; alpha 4 beta 1-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.
Nakajima
S
S
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Look
D C
DC
Roswit
W T
WT
Bragdon
M J
MJ
Holtzman
M J
MJ
D015815:Cell Adhesion Molecules / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology*; D004847:Epithelial Cells; D005434:Flow Cytometry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*; D014132:Trachea / Q000166:cytology*; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1