Nature Immunology5, 583 - 589 (2004)
Published online: 9 May 2004; | doi:10.1038/ni1071
A Bcl-2-dependent molecular timer regulates the lifespan and immunogenicity of dendritic cells
Wu-Shiun Hou
& Luk Van Parijs
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Correspondence should be addressed to Luk Van Parijs lukvp@mit.edu
The lifespan of antigen-bearing dendritic cells (DCs) is determined by signals from pathogens and T cells. These signals regulate DC survival by modulating expression of Bcl-2 family proteins. Toll-like receptors and T cell costimulatory molecules both trigger a DC survival pathway that is dependent on Bcl-xL. However, Toll-like receptors uniquely increase expression of Bim and trigger cell death by a pathway that is blocked by Bcl-2. This pathway serves as a molecular 'timer' that sets the lifespan of DCs and regulates the magnitude of T cell responses in vivo. Thus, signals derived from the innate and acquired immune systems control DC lifespan and immunogenicity by distinct molecular mechanisms.
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