The long isoform of cellular FLIP is essential for T lymphocyte proliferation through an NF-kappaB-independent pathway

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

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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:
Animals
CASP8 and FADD-Like Apoptosis Regulating Protein - chemistry
CASP8 and FADD-Like Apoptosis Regulating Protein - genetics
CASP8 and FADD-Like Apoptosis Regulating Protein - immunology
CASP8 and FADD-Like Apoptosis Regulating Protein - metabolism
Cell Proliferation
Interleukin-2 - metabolism
Lymphocyte Activation
Mice
Mice, Knockout
Mitogen-Activated Protein Kinase Kinases - immunology
Mitogen-Activated Protein Kinase Kinases - metabolism
NF-kappa B - metabolism
Protein Isoforms - chemistry
Protein Isoforms - immunology
Protein Isoforms - metabolism
Receptors, Antigen, T-Cell - immunology
Receptors, Antigen, T-Cell - metabolism
T-Lymphocytes - immunology
T-Lymphocytes - physiology
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Summary:Although the long isoform of cellular FLIP (c-FLIP(L)) has been implicated in TCR-mediated signaling, its role in T cell proliferation remains controversial. Some studies have demonstrated that overexpression of c-FLIP(L) promotes T cell proliferation and NF-kappaB activation, whereas others have reported that c-FLIP(L) overexpression has no effect or even inhibits T cell proliferation. To establish the role of c-FLIP(L) in T lymphocyte proliferation, we have generated a conditional knockout mouse strain specifically lacking c-FLIP(L) in T lymphocytes. c-FLIP(L)(-/-) mice exhibit severely impaired effector T cell development after Listeria monocytogenes infection in vivo and c-FLIP(L)-deficient T cells display defective TCR-mediated proliferation in vitro. However, c-FLIP(L)(-/-) T cells exhibit normal NF-kappaB activity upon TCR stimulation. These results demonstrate that c-FLIP(L) is essential for T lymphocyte proliferation through an NF-kappaB-independent pathway.
ISSN:0022-1767