First Author | Zhang N | Year | 2008 |
Journal | J Immunol | Volume | 180 |
Issue | 8 | Pages | 5506-11 |
PubMed ID | 18390734 | Mgi Jnum | J:134252 |
Mgi Id | MGI:3785193 | Doi | 10.4049/jimmunol.180.8.5506 |
Citation | Zhang N, et al. (2008) The long isoform of cellular FLIP is essential for T lymphocyte proliferation through an NF-kappaB-independent pathway. J Immunol 180(8):5506-11 |
abstractText | 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. |