c-FLIP protects mature T lymphocytes from TCR-mediated killing.
Although c-FLIP has been identified as an important player in the extrinsic (death receptor-induced) apoptosis pathway, its endogenous function in mature T lymphocytes remains undefined. c-FLIP may inhibit or promote T cell death as previous data demonstrate that the c-FLIP(L) isoform can promote or inhibit caspase 8 activation while the c-FLIP(S) isoform promotes or inhibits T cell death when overexpressed. Although the c-FLIP(R) isoform inhibits cell death in cell lines, its function in T cells remains unknown. To investigate the function of c-FLIP in mature T cells, we have generated several genetic mouse models with c-FLIP or its individual isoforms deleted in mature T cells. Surprisingly, we found that c-FLIP protects mature T cells not only from apoptosis induced by the death receptors Fas and TNFR but also from TCR-mediated and spontaneous apoptosis. Thus, c-FLIP plays an essential role in protecting mature T cells from a death signal induced through the TCR itself and is required for naive T cell survival. Our results demonstrate that c-FLIP functions beyond the extrinsic death pathway.
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- fas Receptor
- T-Lymphocytes
- Receptors, Antigen, T-Cell
- Protein Isoforms
- Models, Immunological
- Mice, Transgenic
- Mice
- Immunology
- Caspase 8
- CASP8 and FADD-Like Apoptosis Regulating Protein
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- fas Receptor
- T-Lymphocytes
- Receptors, Antigen, T-Cell
- Protein Isoforms
- Models, Immunological
- Mice, Transgenic
- Mice
- Immunology
- Caspase 8
- CASP8 and FADD-Like Apoptosis Regulating Protein