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TCR-mediated up-regulation of c-FLIPshort correlates with resistance toward CD95-mediated apoptosis by blocking death-inducing signaling complex activity

To investigate apoptosis resistance upon restimulation in human peripheral blood T lymphocytes, we used the following in vitro model. This model represents the main features of T cell reactivity: freshly isolated PHA-activated T cells cultured in IL-2 for a prolonged period of time develop a CD95 (A...

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Hauptverfasser: Kirchhoff, Sabine (VerfasserIn) , Krammer, Peter H. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: December 1, 2000
In: The journal of immunology
Year: 2000, Jahrgang: 165, Heft: 11, Pages: 6293-6300
ISSN:1550-6606
DOI:10.4049/jimmunol.165.11.6293
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.4049/jimmunol.165.11.6293
Verlag, lizenzpflichtig, Volltext: https://www-jimmunol-org.ubproxy.ub.uni-heidelberg.de/content/165/11/6293
Volltext
Verfasserangaben:Sabine Kirchhoff, Wolfgang W. Müller, Andreas Krueger, Ingo Schmitz, and Peter H. Krammer
Beschreibung
Zusammenfassung:To investigate apoptosis resistance upon restimulation in human peripheral blood T lymphocytes, we used the following in vitro model. This model represents the main features of T cell reactivity: freshly isolated PHA-activated T cells cultured in IL-2 for a prolonged period of time develop a CD95 (APO-1/Fas) apoptosis-sensitive phenotype. These T cells represent activation-induced cell death-sensitive T cells during the down phase of an immune response. A fraction of apoptosis-sensitive activated T cells becomes apoptosis resistant upon TCR/CD3 restimulation. CD95 apoptosis sensitivity requires formation of a functional receptor associated death-inducing signaling complex (DISC), i.e., a protein complex of CD95 receptors, the adaptor Fas-associated death domain protein (FADD)/MORT1 and caspase-8 (FADD-like IL-1β-converting enzyme (FLICE), MACH, Mch5). We identified activation of procaspase-8 at the DISC as the main target for the protective activity of TCR/CD3 restimulation. We found that procaspase-8 cleavage is reduced in T cells after TCR/CD3 restimulation. In addition, we detected up-regulation of c-FLIPS (the short splice variant of the cellular FLICE inhibitory protein) and strongly enhanced recruitment of c-FLIPS into the DISC. These data suggest that the recruitment of c-FLIPS into the DISC results in reduced DISC and caspase-8 activity.
Beschreibung:Gesehen am 26.04.2021
Im Titel ist der Ausdruck "short" tiefgestellt
Beschreibung:Online Resource
ISSN:1550-6606
DOI:10.4049/jimmunol.165.11.6293

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