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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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
December 1, 2000
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| In: |
The journal of immunology
Year: 2000, Volume: 165, Issue: 11, Pages: 6293-6300 |
| ISSN: | 1550-6606 |
| DOI: | 10.4049/jimmunol.165.11.6293 |
| Online Access: | 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 
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| Author Notes: | Sabine Kirchhoff, Wolfgang W. Müller, Andreas Krueger, Ingo Schmitz, and Peter H. Krammer |
| Summary: | 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. |
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| Item Description: | Gesehen am 26.04.2021 Im Titel ist der Ausdruck "short" tiefgestellt |
| Physical Description: | Online Resource |
| ISSN: | 1550-6606 |
| DOI: | 10.4049/jimmunol.165.11.6293 |