CCR7 ligands control basal T cell motility within lymph node slices in a phosphoinositide 3-kinase-independent manner

J Exp Med. 2007 May 14;204(5):1167-79. doi: 10.1084/jem.20062079. Epub 2007 May 7.

Abstract

The molecular mechanisms responsible for the sustained basal motility of T cells within lymph nodes (LNs) remain elusive. To study T cell motility in a LN environment, we have developed a new experimental system based on slices of LNs that allows the assessment of T cell trafficking after adoptive transfer or direct addition of T cells to the slice. Using this experimental system, we show that T cell motility is highly sensitive to pertussis toxin and strongly depends on CCR7 and its ligands. Our results also demonstrate that, despite its established role in myeloid cell locomotion, phosphoinositide 3-kinase (PI3K) activity does not contribute to the exploratory behavior of the T lymphocytes within LN slices. Likewise, although PI3K activation is detectable in chemokine-treated T cells, PI3K plays only a minor role in T cell polarization and migration in vitro. Collectively, our results suggest that the common amplification system that, in other cells, facilitates large phosphatidylinositol 3,4,5-trisphosphate increases at the plasma membrane is absent in T cells. We conclude that T cell motility within LNs is not an intrinsic property of T lymphocytes but is driven in a PI3K-independent manner by the lymphoid chemokine-rich environment.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Calcium / metabolism
  • Cell Movement / drug effects
  • Cell Movement / immunology*
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Ligands
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Pertussis Toxin / toxicity
  • Phosphatidylinositol 3-Kinases / metabolism
  • Receptors, CCR7 / metabolism*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Transfection

Substances

  • CCR7 protein, human
  • Ligands
  • Receptors, CCR7
  • Pertussis Toxin
  • Phosphatidylinositol 3-Kinases
  • Calcium