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Amplification of Fas-mediated apoptosis in type II cells via microdomain recruitment

Patrick Legembre1, Sophie Daburon, Patrick Moreau

  • 1Laboratoire CIRID, CNRS UMR 5164, Université de Bordeaux 2, 146 rue Léo Saignat, Bordeaux 33076, France.

Molecular and Cellular Biology
|July 19, 2005
PubMed

Insights

Co-ligation with CD28 enhances Fas-induced apoptosis in type II T lymphocytes by recruiting Fas to lipid rafts. This mechanism amplifies cell death signaling in type II cells, independent of intracellular CD28 signaling.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Fas receptor triggers apoptosis through the caspase cascade upon binding Fas ligand (FasL).
  • In type I cells, Fas localization in lipid rafts is crucial for apoptosis.
  • In type II cells, Fas is typically excluded from lipid rafts, limiting apoptosis sensitivity.

Purpose of the Study:

  • To investigate the role of CD28 co-stimulation in modulating Fas-induced apoptosis in type II T lymphocytes.
  • To determine the mechanism by which CD28 influences Fas-mediated cell death.

Main Methods:

  • Utilized type I and type II cell lines.
  • Investigated the effect of CD28 co-ligation with Fas on apoptosis.
  • Examined Fas redistribution into lipid rafts upon CD28 stimulation.
  • Disrupted lipid rafts using a cholesterol chelator to assess their role.

Main Results:

  • CD28 co-ligation significantly enhanced Fas-induced apoptosis in type II T lymphocytes, but not in type I cells.
  • This enhancement was independent of the intracellular region of CD28.
  • CD28 stimulation induced the recruitment of Fas into lipid rafts.
  • Disruption of lipid rafts abrogated the CD28-mediated amplification of apoptosis.
  • The amplified cell death involved enhancement of the mitochondrial apoptotic pathway.

Conclusions:

  • CD28 co-stimulation amplifies Fas-induced apoptosis in type II cells by recruiting Fas to lipid rafts.
  • This microdomain-mediated amplification enhances the mitochondrial apoptotic pathway.
  • Interactions involving non-apoptotic ligand/receptor pairs can modulate Fas sensitivity in vivo.

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