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 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.
Zhang
Nu
N
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Hopkins
Kaycie
K
He
You-Wen
YW
D000818:Animals; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D049109:Cell Proliferation; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D020929:Mitogen-Activated Protein Kinase Kinases / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D007376:Interleukin-2; D016328:NF-kappa B; D020033:Protein Isoforms; D011948:Receptors, Antigen, T-Cell; D020929:Mitogen-Activated Protein Kinase Kinases