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

M Maksimow, TS Söderström, S Jalkanen, John Eriksson, A Hänninen

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    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.
    Original languageUndefined/Unknown
    Pages (from-to)369–377
    JournalJournal of Leukocyte Biology
    Issue number2
    Publication statusPublished - 2006
    MoE publication typeA1 Journal article-refereed

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