FADD and the NF-kappa B family member Bcl-3 regulate complementary pathways to control T-cell survival and proliferation

Rangelova, S; Kirschnek, S; Strasser, A; Hacker, G

Author(s): Rangelova, S; Kirschnek, S; Strasser, A; Hacker, G;
Details: Publication Year 2008-12,Volume 125,Issue #4,Page 549-557
Journal Title: IMMUNOLOGY
Publication Type: Journal Article
Abstract: Fas-associated protein with death domain/mediator of receptor induced toxicity (FADD/MORT1) was first described as a transducer of death receptor signalling but was later recognized also to be important for proliferation of T cells. B-cell lymphoma 3 (Bcl-3) is a relatively little understood member of the nuclear factor (NF)-kappa B family of transcription factors. We recently found that Bcl-3 is up-regulated in T cells from mice where FADD function is blocked by a dominant negative transgene (FADD-DN). To understand the importance of this, we generated FADD-DN/bcl-3(-/-) mice. Here, we report that T cells from these mice show massive cell death and severely reduced proliferation in response to T-cell receptor (TCR) stimulation in vitro. Transgenic co-expression of Bcl-2 (FADD-DN/bcl-3(-/-)/vav-bcl-2 mice) rescued the survival but not the proliferation of T cells. FADD-DN/bcl-3(-/-) mice had normal thymocyte numbers but reduced numbers of peripheral T cells despite an increase in cycling T cells in vivo. However, activation of the classical NF-kappa B and extracellular regulated kinase (ERK) pathways and expression of interleukin (IL)-2 mRNA upon stimulation were normal in T cells from FADD-DN/bcl-3(-/-) mice. These data suggest that FADD and Bcl-3 regulate separate pathways that both contribute to survival and proliferation in mouse T cells.
Publisher: WILEY-BLACKWELL
Keywords: DOMINANT INTERFERING MUTANT; MEDIATED-IMMUNITY; BH3-ONLY PROTEINS; C-FLIP; CASPASE-8; DEATH; APOPTOSIS; ACTIVATION; LYMPHOCYTES; FADD/MORT1
Publisher's Version: https://doi.org/10.1111/j.1365-2567.2008.02869.x
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Creation Date: 2008-12-01 12:00:00