Fas costimulation of naive CD4 T cells is controlled by NF-kappaB signaling and caspase activity

J Leukoc Biol. 2006 Feb;79(2):369-77. doi: 10.1189/jlb.0505238. Epub 2005 Dec 5.

Abstract

Fas ligation induces apoptosis of activated T cells via the caspase cascade but can also mediate costimulatory signals to naïve T cells at the time of activation. We have previously shown that Fas ligation of naïve CD4 T cells activated by dendritic cells induces death or accelerates their proliferation and increases interferon-gamma (IFN-gamma) production. To understand this costimulation, we investigated the roles of caspases and nuclear factor (NF)-kappaB in survival and proliferation of responding T cells. Fas ligation increased caspase-3 and -8 activities during T cell activation, irrespective of cell fate. The accelerated proliferation induced by Fas ligation could be reduced by selective inhibition of both caspases. Inhibition of NF-kappaB simultaneously with Fas ligation inhibited the increased IFN-gamma production and caused uniform death of all responding T cells. Thus, Fas-mediated costimulation of naïve CD4 T cells is driven by active caspases, and NF-kappaB acts as a dominant survival-supporting factor of Fas-costimulated cells containing high levels of activated caspase-8 and -3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / immunology
  • Caspase 3
  • Caspase 8
  • Caspases / drug effects
  • Caspases / immunology*
  • Caspases / metabolism*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Fas Ligand Protein
  • Interferon-gamma / antagonists & inhibitors
  • Interferon-gamma / biosynthesis
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / pharmacology*
  • Mice
  • NF-kappa B / pharmacology
  • NF-kappa B / physiology*
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Tumor Necrosis Factor Inhibitors
  • Tumor Necrosis Factors / pharmacology*

Substances

  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • NF-kappa B
  • Tumor Necrosis Factor Inhibitors
  • Tumor Necrosis Factors
  • Interferon-gamma
  • Casp3 protein, mouse
  • Casp8 protein, mouse
  • Caspase 3
  • Caspase 8
  • Caspases