Resistance of short term activated T cells to CD95-mediated apoptosis correlates with de novo protein synthesis of c-FLIPshort

In the early phase of an immune response, T cells are activated and acquire effector functions. Whereas these short term activated T cells are resistant to CD95-mediated apoptosis, activated T cells in prolonged culture are readily sensitive, leading to activation-induced cell death and termination...

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Main Authors: Schmitz, Ingo (Author) , Weyd, Heiko (Author) , Krueger, Andreas (Author) , Baumann, Sven (Author) , Fas, Stefanie C. (Author) , Krammer, Peter H. (Author) , Kirchhoff, Sabine (Author)
Format: Article (Journal)
Language:English
Published: 5 February 2004
In: The journal of immunology
Year: 2004, Volume: 172, Issue: 4, Pages: 2194-2200
ISSN:1550-6606
DOI:10.4049/jimmunol.172.4.2194
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.4049/jimmunol.172.4.2194
Verlag, lizenzpflichtig, Volltext: https://www.jimmunol.org/content/172/4/2194
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Author Notes:Ingo Schmitz, Heiko Weyd, Andreas Krueger, Sven Baumann, Stefanie C. Fas, Peter H. Krammer, and Sabine Kirchhoff
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Summary:In the early phase of an immune response, T cells are activated and acquire effector functions. Whereas these short term activated T cells are resistant to CD95-mediated apoptosis, activated T cells in prolonged culture are readily sensitive, leading to activation-induced cell death and termination of the immune response. The translation inhibitor, cycloheximide, partially overcomes the apoptosis resistance of short term activated primary human T cells. Using this model we show in this study that sensitization of T cells to apoptosis occurs upstream of mitochondria. Neither death-inducing signaling complex formation nor expression of Bcl-2 proteins is altered in sensitized T cells. Although the caspase-8 inhibitor c-FLIPlong was only slightly down-regulated in sensitized T cells, c-FLIPshort became almost undetectable. This correlated with caspase-8 activation and apoptosis. These data suggest that c-FLIPshort, rather than c-FLIPlong, confers resistance of T cells to CD95-mediated apoptosis in the context of immune responses.
Item Description:Im Titel ist "short" bei c-FLIP tiefgestellt
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Physical Description:Online Resource
ISSN:1550-6606
DOI:10.4049/jimmunol.172.4.2194