Antigen presentation by human microvascular endothelial cells triggers ICAM-1-dependent transendothelial protrusion by, and fractalkine-dependent transendothelial migration of, effector memory CD4+ T cells

J Immunol. 2008 Jun 15;180(12):8386-92. doi: 10.4049/jimmunol.180.12.8386.

Abstract

TCR engagement on adherent human effector memory CD4(+) T cells by TNF-treated HUVECs under flow induces formation of a transendothelial protrusion (TEP) by the T cell but fails to induce transendothelial migration (TEM). In contrast, TCR engagement of the same T cell populations by TNF-treated human dermal microvascular cells (HDMEC) not only induces TEP formation, but triggers TEM at or near the interendothelial cell junctions via a process in which TEP formation appears to be the first step. Transduction of adhesion molecules in unactivated HDMEC and use of blocking Abs as conducted with TNF-activated HDMEC indicate that ICAM-1 plays a nonredundant role in TCR-driven TEP formation and TEM, and that TCR-driven TEM is also dependent upon fractalkine. TEP formation, dependence on ICAM-1, and dependence on fractalkine distinguish TCR-induced TEM from IP-10-induced TEM. These in vitro observations suggest that presentation of Ag by human microvascular endothelial cells to circulating CD4(+) effector memory T cells may function to initiate recall responses in peripheral tissues.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigen Presentation / immunology*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Migration Inhibition / immunology
  • Cell Movement / immunology*
  • Cells, Cultured
  • Chemokine CX3CL1 / physiology*
  • Chemokine CXCL10 / physiology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / immunology*
  • Endothelium, Vascular / metabolism*
  • Humans
  • Immunologic Memory*
  • Intercellular Adhesion Molecule-1 / physiology*
  • Microcirculation / cytology
  • Microcirculation / immunology
  • Microcirculation / metabolism
  • Nuclear Proteins / genetics
  • Receptors, Antigen, T-Cell / biosynthesis
  • Receptors, Antigen, T-Cell / physiology
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Shear Strength
  • Skin / blood supply
  • Skin / cytology
  • Skin / immunology
  • Skin / metabolism
  • Trans-Activators / genetics
  • Transduction, Genetic

Substances

  • CX3CL1 protein, human
  • CXCL10 protein, human
  • Chemokine CX3CL1
  • Chemokine CXCL10
  • MHC class II transactivator protein
  • Nuclear Proteins
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, alpha-beta
  • Trans-Activators
  • Intercellular Adhesion Molecule-1