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 language | English (US) |
|---|---|
| Pages (from-to) | 5368-5373 |
| Number of pages | 6 |
| Journal | Journal of Immunology |
| Volume | 181 |
| Issue number | 8 |
| DOIs | |
| State | Published - Jan 1 2008 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
c-FLIP protects mature T lymphocytes from TCR-mediated killing. / Zhang, Nu; Hopkins, Kaycie; He, You Wen.
In: Journal of Immunology, Vol. 181, No. 8, 01.01.2008, p. 5368-5373.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - c-FLIP protects mature T lymphocytes from TCR-mediated killing
AU - Zhang, Nu
AU - Hopkins, Kaycie
AU - He, You Wen
PY - 2008/1/1
Y1 - 2008/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=54049130409&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=54049130409&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.181.8.5368
DO - 10.4049/jimmunol.181.8.5368
M3 - Article
C2 - 18832693
AN - SCOPUS:54049130409
VL - 181
SP - 5368
EP - 5373
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 8
ER -