Four molecular pathways of T cell adhesion to endothelial cells: roles of LFA-1, VCAM-1, and ELAM-1 and changes in pathway hierarchy under different activation conditions

J Cell Biol. 1991 Jun;113(5):1203-12. doi: 10.1083/jcb.113.5.1203.


T cell adhesion to endothelium is critical to lymphocyte recirculation and influx into sites of inflammation. We have systematically analyzed the role of four receptor/ligand interactions that mediate adhesion of peripheral human CD4+ T cells to cultured human umbilical vein endothelial cells (HUVEC): T cell LFA-1 binding to ICAM-1 and an alternative ligand ("ICAM-X"), T cell VLA-4 binding to VCAM-1, and T cell binding to ELAM-1. Contributions of these four pathways depend on the activation state of both the T cell and HUVEC, and the differentiation state of the T cell. ELAM-1 plays a significant role in mediating adhesion of resting CD4+ T cells to activated HUVEC. LFA-1 adhesion dominates with PMA-activated T cells but the strength and predominant LFA-1 ligand is determined by the activation state of the HUVEC; while ICAM-1 is the dominant ligand on IL-1-induced HUVEC, "ICAM-X" dominates binding to uninduced HUVEC. Adhesion via VLA-4 depends on induction of its ligand VCAM-1 on activated HUVEC; PMA activation of T cells augments VLA-4-mediated adhesion, both in the model of T/HUVEC binding and in a simplified model of T cell adhesion to VCAM-1-transfected L cells. Unlike LFA-1 and VLA-4, ELAM-1-mediated adhesion is not increased by T cell activation. Differential expression of adhesion molecules on CD4+ T cell subsets understood to be naive and memory cells also regulates T/HUVEC adhesion. Naive T cell adhesion to HUVEC is mediated predominantly by LFA-1 with little or no involvement of the VLA-4 and ELAM-1 pathways. In contrast, memory T cells bind better to HUVEC and utilize all four pathways. These studies demonstrate that there are at least four molecular pathways mediating T/HUVEC adhesion and that the dominance/hierarchy of these pathways varies dramatically with the activation state of the interacting cells and the differentiation state of the T cell.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / physiology
  • CD4 Antigens / analysis
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / physiology*
  • Cell Adhesion*
  • Cells, Cultured
  • E-Selectin
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology*
  • Humans
  • Intercellular Adhesion Molecule-1
  • L Cells / physiology
  • Ligands
  • Lymphocyte Function-Associated Antigen-1 / physiology*
  • Mice
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / physiology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / physiology*
  • Transfection
  • Vascular Cell Adhesion Molecule-1


  • Antigens, CD
  • CD4 Antigens
  • Cell Adhesion Molecules
  • E-Selectin
  • Ligands
  • Lymphocyte Function-Associated Antigen-1
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1