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FADD and the NF‐κB family member Bcl‐3 regulate complementary pathways to control T‐cell survival and proliferation
Author(s) -
Rangelova Svetla,
Kirschnek Susanne,
Strasser Andreas,
Häcker Georg
Publication year - 2008
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2008.02869.x
Subject(s) - fadd , biology , death domain , microbiology and biotechnology , thymocyte , programmed cell death , mapk/erk pathway , signal transduction , t cell , apoptosis , cell growth , cancer research , immunology , caspase , immune system , biochemistry
Summary 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)‐κB 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‐κB 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.