The Long Isoform of Cellular FLIP Is Essential for T Lymphocyte Proliferation through an NF-κB-Independent Pathway

Although the long isoform of cellular FLIP (c-FLIPL) has been implicated in TCR-mediated signaling, its role in T cell proliferation remains controversial. Some studies have demonstrated that overexpression of c-FLIPL promotes T cell proliferation and NF-κB activation, whereas others have reported t...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2008-04, Vol.180 (8), p.5506-5511
Main Authors: Zhang, Nu, Hopkins, Kaycie, He, You-Wen
Format: Article
Language:English
Subjects:
Listeria monocytogenes
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Summary:Although the long isoform of cellular FLIP (c-FLIPL) has been implicated in TCR-mediated signaling, its role in T cell proliferation remains controversial. Some studies have demonstrated that overexpression of c-FLIPL promotes T cell proliferation and NF-κB activation, whereas others have reported that c-FLIPL overexpression has no effect or even inhibits T cell proliferation. To establish the role of c-FLIPL in T lymphocyte proliferation, we have generated a conditional knockout mouse strain specifically lacking c-FLIPL in T lymphocytes. c-FLIPL−/− mice exhibit severely impaired effector T cell development after Listeria monocytogenes infection in vivo and c-FLIPL-deficient T cells display defective TCR-mediated proliferation in vitro. However, c-FLIPL−/− T cells exhibit normal NF-κB activity upon TCR stimulation. These results demonstrate that c-FLIPL is essential for T lymphocyte proliferation through an NF-κB-independent pathway.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.180.8.5506