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Published online before print December 5, 2005

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0505238

Received for publication May 4, 2005.
Revised October 18, 2005.
Accepted for publication October 19, 2005.

Article

Fas costimulation of naïve CD4 T cells is controlled by NF-B signaling and caspase activity

Mikael Maksimow ^*, Thomas S. Söderström , Sirpa Jalkanen ^*, John E. Eriksson ^¶, and Arno Hänninen ^*@

*MediCity Research Laboratory and Department of Medical Microbiology, University of Turku, and National Public Health Institute, Turku, Finland; Turku Centre for Biotechnology, University of Turku, and Åbo Akademi University, Finland; Department of Biology, Åbo Akademi University, Turku, Finland; ^¶Department of Biology, Laboratory of Animal Physiology, University of Turku, Finland; and Turku Graduate School of Biomedical Sciences, Finland

^@ To whom correspondence should be addressed. E-mail: arno.hanninen{at}utu.fi.

	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- (IFN-) production. To understand this costimulation, we investigated the roles of caspases and nuclear factor (NF)-B 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. It is interesting that inhibition of NF-B simultaneously with Fas ligation inhibited the increased IFN- 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-B acts as a dominant survival-supporting factor of Fas-costimulated cells containing high levels of activated caspase-8 and -3.

Key Words: T cell activation • lymphocyte • apoptosis • dendritic cell • cell proliferation

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