Differential usage of VLA-4 and CXCR4 by CD3+CD56+ NKT cells and CD56+CD16+ NK cells regulates their interaction with endothelial cells

Suzanna Franitza, Valentin Grabovsky, Ori Wald, Ido Weiss, Katia Beider, Michal Dagan, Merav Darash-Yahana, Arnon Nagler, Stefan Brocke, Eithan Galun, Ronen Alon, Amnon Peled*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

The mechanism that regulates the preferential accumulation of NKT cells in the BM is unknown. The BM endothelium constitutively expresses selectins, the integrin ligands VCAM-1 and ICAM-1, and the chemokine CXCL12. Both NK and NKT subsets of cells exhibited similar tethering and rolling interactions on both P-selectin and E-selectin and expressed similar levels of the integrins, VLA-4 and LFA-1. Although NKT cells express higher levels of CXCR4 than NK cells, CXCL12 (the ligand for CXCR4) rapidly stimulates similar levels of adhesion of NK and NKT cells to VCAM-1 and ICAM-1. In both subsets, the arrest on VCAM-1 was dependent on high affinity VLA-4 and the homing of these cells to the BM of NOD/SCID was VLA-4-dependent. However, as opposed to the situation for NK cells, CXCL12 preferentially triggers, under shear flow, the rolling on VCAM-1 and transendothelial migration of NKT cells. Moreover, over-expression of high levels of CXCR4 on the YT NK cell line enables them to migrate in response to CXCL12. This study therefore suggests an important role for CXCR4 levels of expression and for VLA-4 in regulating the accumulation of NKT cells in the BM.

Original languageAmerican English
Pages (from-to)1333-1341
Number of pages9
JournalEuropean Journal of Immunology
Volume34
Issue number5
DOIs
StatePublished - May 2004
Externally publishedYes

Keywords

  • CXCR4
  • Endothelial cell
  • NK cell
  • VLA-4

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