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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Zhang, N; Hopkins, K; He, Y-W

Published Date

  • 2008-10-15

Published In

Volume / Issue

  • 181 / 8

Start / End Page

  • 5368 - 5373

PubMed ID

  • 18832693

Pubmed Central ID

  • 18832693

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.181.8.5368

Language

  • eng

Conference Location

  • United States