Document Detail


Cutting edge: abortive proliferation of CD46-induced Tr1-like cells due to a defective Akt/Survivin signaling pathway.
MedLine Citation:
PMID:  17015676     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
T regulatory cell 1 (Tr1) are low proliferating peripherally induced suppressive T cells. Engaging CD3 and CD46 on human CD4+ T cells induces a Tr1-like phenotype. In this study, we report that human Tr1-like cells do not sustain proliferation over time. The weak proliferation of these cells results first from their inability to sustain expression of various cell cycle-associated proteins, to efficiently degrade the inhibitor of cell cycle progression p27/Kip1 and, as a consequence, in their accumulation in the G0-G1 phase. Also, the reduced proliferation of Tr1-like cells results from their increased sensitivity to death as they divide, through a mechanism that is neither Fas-mediated nor Bcl2/Bcl-xL related. Both properties, impaired cell cycle and death sensitivity, are explained by a specific defective activation of Akt that impairs the expression of Survivin. Thus, our results show that CD3/CD46-induced Tr1-like cells die through a process of abortive proliferation.
Authors:
Grégory Meiffren; Monique Flacher; Olga Azocar; Chantal Rabourdin-Combe; Mathias Faure
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  177     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-10-03     Completed Date:  2007-02-06     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4957-61     Citation Subset:  AIM; IM    
Affiliation:
Institut National de la Santé et de la Recherche Médicale Unité 503-IFR 128-BioSciences Lyon-Gerland-Université Claude-Bernard-Lyon 1, Lyon, France.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD3 / physiology
Antigens, CD46 / physiology*
Cell Cycle
Cell Death
Cell Proliferation*
Humans
Intracellular Signaling Peptides and Proteins / metabolism
Microtubule-Associated Proteins / physiology*
Neoplasm Proteins / physiology*
Proto-Oncogene Proteins c-akt / physiology*
Signal Transduction*
T-Lymphocytes, Regulatory / cytology*
Chemical
Reg. No./Substance:
0/Antigens, CD3; 0/Antigens, CD46; 0/BIRC5 protein, human; 0/CDKN1B protein, human; 0/Intracellular Signaling Peptides and Proteins; 0/Microtubule-Associated Proteins; 0/Neoplasm Proteins; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

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


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