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J Immunol. 2008 Apr 15;180(8):5506-11.

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

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1
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.

Abstract

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.

PMID:
18390734
[Indexed for MEDLINE]
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