Document Detail

Apoptosis regulators Fas and Bim synergistically control T-lymphocyte homeostatic proliferation.
MedLine Citation:
PMID:  20979227     Owner:  NLM     Status:  Publisher    
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.
Karen A Fortner; Philippe Bouillet; Andreas Strasser; Ralph C Budd
Related Documents :
9454907 - Fas (apo-1/cd95)-mediated apoptosis is independent of bcl-2: a study with cell lines ov...
20148857 - Asperfuranone from aspergillus nidulans inhibits proliferation of human non-small cell ...
9389707 - Functional expression of fas (cd95) in acute myeloid leukemia cells in the context of c...
11478767 - Apoptosis induction by epigallocatechin gallate involves its binding to fas.
21692747 - Modulation of microtubule dynamics by a tir domain protein from the intracellular patho...
3009637 - The histopathology of experimental trachoma: ultrastructural changes in the conjunctiva...
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:  -    
Vermont Center for Immunology and Infectious Disease, The University of Vermont College of Medicine, Burlington, VT, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Interferon regulatory factor 4 regulates thymocyte differentiation by repressing Runx3 expression.
Next Document:  T-cell-specific deletion of STIM1 and STIM2 protects mice from EAE by impairing the effector functio...