Fas stimulation of T lymphocytes promotes rapid intercellular exchange of death signals via membrane nanotubes

Cell Res. 2010 Jan;20(1):72-88. doi: 10.1038/cr.2009.112. Epub 2009 Sep 22.

Abstract

The Fas/CD95 surface receptor mediates rapid death of various cell types, including autoreactive T cells with the potential for triggering autoimmunity. Here, we present novel aspects of Fas signalling that define a 'social' dimension to receptor-induced apoptosis. Fas stimulation rapidly induces extensive membrane nanotube formation between neighbouring T cells. This is critically dependent on Rho GTPases but not on caspase activation. Bidirectional transfer of membrane and cytosolic elements including active caspases can be observed to occur via these nanotubes. Nanotube formation and intercellular exchanges of death signals are defective in T lymphocytes from patients with autoimmune lymphoproliferative syndrome harbouring mutations in the Fas receptor. We conclude that nanotube-mediated exchanges constitute a novel form of intercellular communication that augments the propagation of death signalling between neighbouring T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • Autoimmune Lymphoproliferative Syndrome / immunology
  • Autoimmune Lymphoproliferative Syndrome / pathology
  • Autoimmune Lymphoproliferative Syndrome / physiopathology
  • Caspases / metabolism
  • Cell Communication / physiology*
  • Cell Line
  • Cell Surface Extensions / immunology*
  • Cell Surface Extensions / ultrastructure*
  • Cells, Cultured
  • Extracellular Space / metabolism
  • Fluorescent Antibody Technique
  • Humans
  • Jurkat Cells
  • Microscopy, Electron, Transmission
  • Nanotubes, Peptide / ultrastructure*
  • Protein Transport / physiology
  • Signal Transduction / physiology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / ultrastructure*
  • fas Receptor / metabolism*
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism

Substances

  • Nanotubes, Peptide
  • fas Receptor
  • Caspases
  • rho GTP-Binding Proteins