期刊
IMMUNOLOGY
卷 125, 期 4, 页码 549-557出版社
WILEY
DOI: 10.1111/j.1365-2567.2008.02869.x
关键词
apoptosis; Bcl-3; FADD; proliferation; T cell
类别
资金
- Deutsche Forschungsgemeinschaft [SFB 391]
- National Health and Medical Research Council [257502]
- Leukemia and Lymphoma Society [7015]
- National Cancer Institute (NIH, US [CA 80188, CA 43540]
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.
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