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Apoptosis regulators Fas and Bim synergistically control T-lymphocyte homeostatic proliferation.
MedLine Citation:
PMID:  20979227     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The size of the peripheral T-lymphocyte compartment is governed by complex homeostatic mechanisms that balance T-cell proliferation and death. Proliferation and survival signals are mediated in part by recurrent self-peptide/MHC-TCR interactions and signaling by the common γ chain-containing cytokine receptors, including those for IL-7 and IL-15. We have previously shown that the death receptor Fas (CD95/APO-1) regulates apoptosis in response to repeated TCR stimulation, whereas the Bcl-2 homology domain 3-only protein Bim mediates cytokine withdrawal-induced apoptosis. We therefore reasoned that these two molecules might cooperate in the regulation of homeostatic proliferation. In this study, we observe that the combined loss of Fas and Bim synergistically enhances the accumulation of T cells in lymphopenic host mice, and this is particularly pronounced for the unusual CD4(-)CD8(-)TCRαβ(+) T cells that are characteristic of Fas-deficient (Fas(lpr/lpr)) mice. Our findings demonstrate that these CD4(-)CD8(-)TCRαβ(+) T cells arise from homeostatic proliferation of CD8(+) T cells. These studies also underscore the profound rate of baseline T-cell proliferation that likely occurs in wild-type mice even in the absence of foreign antigen, and the consequent need for its coordinated regulation by multiple death-signaling pathways.
Authors:
Karen A Fortner; Philippe Bouillet; Andreas Strasser; Ralph C Budd
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2010-9-21
Journal Detail:
Title:  European journal of immunology     Volume:  -     ISSN:  1521-4141     ISO Abbreviation:  -     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-10-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Vermont Center for Immunology and Infectious Disease, The University of Vermont College of Medicine, Burlington, VT, USA.
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