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.
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.
Manes
Thomas D
TD
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Pober
Jordan S
JS
D017951:Antigen Presentation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002464:Cell Migration Inhibition / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D054428:Chemokine CX3CL1 / Q000502:physiology*; D054357:Chemokine CXCL10 / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007156:Immunologic Memory; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D008833:Microcirculation / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000502:physiology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics; D033081:Shear Strength; D012867:Skin / Q000098:blood supply / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics; D014161:Transduction, Genetic
C515538:CX3CL1 protein, human; C114753:CXCL10 protein, human; D054428:Chemokine CX3CL1; D054357:Chemokine CXCL10; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015534:Trans-Activators; D018799:Intercellular Adhesion Molecule-1