| First Author | Zhang N | Year | 2008 |
| Journal | J Immunol | Volume | 181 |
| Issue | 8 | Pages | 5368-73 |
| PubMed ID | 18832693 | Mgi Jnum | J:140768 |
| Mgi Id | MGI:3814519 | Doi | 10.4049/jimmunol.181.8.5368 |
| Citation | Zhang N, et al. (2008) c-FLIP protects mature T lymphocytes from TCR-mediated killing. J Immunol 181(8):5368-73 |
| abstractText | 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. |
