Document Detail


Analysis of gene profile, steady state proliferation and apoptosis of double-negative T cells in the periphery and gut epithelium provides new insights into the biological functions of the Fas pathway.
MedLine Citation:
PMID:  20066510     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Considerable progress has been made in understanding the Fas pathway at the molecular and cellular levels, but fundamental questions about the overall biological role of the Fas pathway remain unresolved. A major question is why lymphoproliferation caused by the lpr mutation of Fas and gld mutation of FasL ligand (FasL) is dominated by CD4(-) and CD8(-) double-negative alphabeta T cells (DN T cells) that are otherwise rare components of the peripheral T cell repertoire. A second unresolved question is why inactivation of the Fas pathway prevents organ-specific autoimmunity (including as type 1 diabetes and multiple sclerosis) while causing systemic lymphoproliferation? Understanding the mechanisms of these processes could uncover important aspects of the biological role of the Fas pathway and could have significant therapeutic implications. For example, revealing the basis of how inactivation of the Fas pathway prevents organ-specific autoimmunity could lead to new immunotherapeutic strategies to promote self tolerance without causing immunosuppression, as the Fas pathway is not essential for T cell activation. Here we discuss recent and new findings from my laboratory that address these questions. On the basis of these findings, we propose a new role for the Fas pathway in sequestration of DN T cells within the gut epithelium.
Authors:
Abdel Rahim A Hamad
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Immunologic research     Volume:  47     ISSN:  1559-0755     ISO Abbreviation:  Immunol. Res.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-23     Completed Date:  2010-10-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8611087     Medline TA:  Immunol Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  134-42     Citation Subset:  IM    
Affiliation:
Department of Pathology, Johns Hopkins University School of Medicine, Ross 659, Baltimore, 21205, USA. ahamad@jhmi.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD95 / genetics,  metabolism*
Apoptosis / physiology*
Cell Proliferation*
Epithelium / immunology
Fas Ligand Protein / genetics,  metabolism
Gene Expression Profiling*
Humans
Intestines / cytology,  immunology*
Lymphocyte Activation
Mice
Mice, Inbred Strains
Mutation
T-Lymphocyte Subsets / cytology*,  immunology
Grant Support
ID/Acronym/Agency:
DK066039 R21/DK/NIDDK NIH HHS; DK069279/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD95; 0/Fas Ligand Protein

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


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