Document Detail


Apoptosis regulators Fas and Bim synergistically control T-lymphocyte homeostatic proliferation.
MedLine Citation:
PMID:  21061436     Owner:  NLM     Status:  MEDLINE    
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; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-27
Journal Detail:
Title:  European journal of immunology     Volume:  40     ISSN:  1521-4141     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-09     Completed Date:  2010-12-17     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  3043-53     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Affiliation:
Vermont Center for Immunology and Infectious Disease, The University of Vermont College of Medicine, Burlington, VT 05405-0068, USA. karen.fortner@uvm.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD95 / agonists,  genetics,  immunology*
Apoptosis / genetics,  immunology*
Apoptosis Regulatory Proteins / agonists,  genetics,  immunology*
CD8-Positive T-Lymphocytes / immunology*
Cell Proliferation*
Histocompatibility Antigens / immunology
Homeostasis / genetics,  immunology*
Interleukin-15 / genetics,  immunology
Interleukin-7 / genetics,  immunology
Membrane Proteins / agonists,  genetics,  immunology*
Mice
Mice, Knockout
Peptides / immunology
Proto-Oncogene Proteins / agonists,  genetics,  immunology*
Receptors, Antigen, T-Cell / genetics,  immunology
Signal Transduction / genetics,  immunology
Grant Support
ID/Acronym/Agency:
AI0797112/AI/NIAID NIH HHS; AI36333/AI/NIAID NIH HHS; R01 AI036333/AI/NIAID NIH HHS; R01 AI036333-04/AI/NIAID NIH HHS; R01 CA043540-22/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD95; 0/Apoptosis Regulatory Proteins; 0/Bcl-2-like protein 11; 0/Fas protein, mouse; 0/Histocompatibility Antigens; 0/Interleukin-15; 0/Interleukin-7; 0/Membrane Proteins; 0/Peptides; 0/Proto-Oncogene Proteins; 0/Receptors, Antigen, T-Cell
Comments/Corrections

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