The chemokine receptor CXCR3 mediates rapid and shear-resistant adhesion-induction of effector T lymphocytes by the chemokines IP10 and Mig

Eur J Immunol. 1998 Mar;28(3):961-72. doi: 10.1002/(SICI)1521-4141(199803)28:03<961::AID-IMMU961>3.0.CO;2-4.


Integrin-mediated adhesion to the vascular endothelium is an essential step in leukocyte diapedesis. We show that the chemokines 10-kDa inflammatory protein (IP10) and monokine induced by IFN (Mig) induce rapid and transient adhesion of human IL-2-stimulated T lymphocytes (IL-2 T cells) to immobilized integrin ligands through their receptor CXCR3, which is selectively expressed on activated T cells. Induction of adhesion by IP10 and Mig was already observed at subnanomolar concentrations and was maximal at 5-10 nM, resulting in three- to sixfold increase in adhesion of IL-2 T cells over background. No effect was seen with resting naive/memory T cells which lack CXCR3 and migration responses to IP10 and Mig. Both chemokines are produced in human umbilical vein endothelial cells (HUVEC) upon stimulation with IFN-gamma and TNF-alpha. These chemokines induce IL-2 T cell adhesion also when captured on the surface of endothelial cells. Under conditions of flow, IL-2 T cells roll and rapidly adhere to IP10/Mig-expressing HUVEC, and anti-CXCR3 mAb treatment reduces arrest and firm adhesion. This is the first study that shows chemokine-induced adhesion in activated memory/effector T cells which represent the fraction of T cells that are selectively mobilized in inflammation. The critical role of IFN-gamma as inducer of IP10/Mig production in HUVEC indicates that these chemokines are essential mediators of effector T cell recruitment to IFN-gamma-dependent pathologies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion
  • Cells, Cultured
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Chemokines, CXC / pharmacology*
  • Endothelium, Vascular / metabolism
  • Humans
  • Integrins / metabolism
  • Intercellular Adhesion Molecule-1 / metabolism
  • Intercellular Signaling Peptides and Proteins*
  • Interferon-gamma / pharmacology
  • Receptors, CXCR3
  • Receptors, Chemokine / physiology*
  • Rheology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Vascular Cell Adhesion Molecule-1 / metabolism


  • CXCL9 protein, human
  • CXCR3 protein, human
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Chemokines, CXC
  • Integrins
  • Intercellular Signaling Peptides and Proteins
  • Receptors, CXCR3
  • Receptors, Chemokine
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Interferon-gamma