Identification of endothelial cell junctional proteins and lymphocyte receptors involved in transendothelial migration of human effector memory CD4+ T cells

J Immunol. 2011 Feb 1;186(3):1763-8. doi: 10.4049/jimmunol.1002835. Epub 2010 Dec 29.

Abstract

Human effector memory (EM) CD4(+) T cells can rapidly transmigrate across an endothelial cell (EC) monolayer in response either to chemokine or to TCR-activating signals displayed by human dermal microvascular EC under conditions of venular shear stress. We previously reported that the TCR-stimulated transendothelial migration (TEM) depends on fractalkine (CX3CL1), PECAM-1 (CD31), and ICAM-1 (CD54) expression by the EC, whereas chemokine-stimulated TEM does not. In this study, we further analyze these responses using blocking mAb and small interfering RNA knockdown to show that TCR-stimulated TEM depends on CD99 on EC as well as on PECAM-1 and depends on nectin-2 (CD112) and poliovirus receptor (CD155) as well as EC ICAM-1. ICAM-1 is engaged by EM CD4(+) T cell LFA-1 (CD11a/CD18) but not Mac-1 (CD11b/CD18); nectin-2 and poliovirus receptor are engaged by both DNAX accessory molecule-1 (CD226) and Tactile (CD96). EC junctional adhesion molecule-1 (JAM-1), an alternative ligand for LFA-1, contributes exclusively to chemokine-stimulated TEM and ICAM-2 appears to be uninvolved in either pathway. These data further define and further highlight the differences in the two pathways of EM CD4(+) T cell recruitment into sites of peripheral inflammation.

Publication types

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

MeSH terms

  • 12E7 Antigen
  • Antibodies, Blocking / pharmacology
  • Antigens, CD / biosynthesis
  • Antigens, CD / metabolism
  • Antigens, CD / physiology
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Adhesion Molecules / antagonists & inhibitors
  • Cell Adhesion Molecules / biosynthesis
  • Cell Adhesion Molecules / immunology
  • Cell Adhesion Molecules / metabolism
  • Cell Adhesion Molecules / physiology*
  • Cell Communication / immunology*
  • Cell Movement / immunology*
  • Cells, Cultured
  • Chemokines / metabolism
  • Chemokines / physiology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / immunology*
  • Endothelium, Vascular / metabolism*
  • Humans
  • Immunologic Memory*
  • Junctional Adhesion Molecules
  • Lymphocyte Function-Associated Antigen-1 / biosynthesis
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Lymphocyte Function-Associated Antigen-1 / physiology
  • Nectins
  • Receptors, Antigen, T-Cell / antagonists & inhibitors
  • Receptors, Antigen, T-Cell / physiology*
  • Receptors, Virus / physiology
  • Signal Transduction / immunology

Substances

  • 12E7 Antigen
  • Antibodies, Blocking
  • Antigens, CD
  • CD99 protein, human
  • Cell Adhesion Molecules
  • Chemokines
  • ICAM2 protein, human
  • Junctional Adhesion Molecules
  • Lymphocyte Function-Associated Antigen-1
  • Nectins
  • Receptors, Antigen, T-Cell
  • Receptors, Virus
  • poliovirus receptor