c-FLIP protects mature T lymphocytes from TCR-mediated killing

Nu Zhang, Kaycie Hopkins, You Wen He

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

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-FLIPL isoform can promote or inhibit caspase 8 activation while the c-FLIPS isoform promotes or inhibits T cell death when overexpressed. Although the c-FLIPR 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.

Original languageEnglish (US)
Pages (from-to)5368-5373
Number of pages6
JournalJournal of Immunology
Volume181
Issue number8
DOIs
Publication statusPublished - Jan 1 2008

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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