Document Detail


The functional insufficiency of human CD4+CD25 high T-regulatory cells in allergic asthma is subjected to TNF-alpha modulation.
MedLine Citation:
PMID:  18053016     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Natural CD4(+)CD25(high)Foxp3(+) regulatory T (nTreg) cells are important in maintaining immunologic tolerance, but their role in the pathogenesis of allergic asthma is unclear. We studied the function of nTreg cells in allergic asthmatic children and assessed the factors which may relate to the functional insufficiency of nTreg cells. METHODS: The percentage of CD4(+)CD25(high) Treg cells, the expression of Foxp3, and the cell-induced suppressive activity of nTreg cells isolated from nonatopic controls, allergic asthmatics, and allergen-specific immunotherapy (AIT)-treated asthmatic patients were studied. RESULTS: Although the percentage of nTreg in peripheral blood mononuclear cells was increased, the expression of Foxp3 and its cell-induced suppressive activity were significantly lower in Dermatophagoides pteronyssinus (Der p)-sensitive asthmatic children when compared to nonatopic controls. In contrast, the expression of Foxp3 and the functional activity of nTreg cells were reversed in allergic asthmatics who received AIT. The addition of recombinant tumor necrosis factor (TNF)-alpha directly downregulated Foxp3 expression and abrogated the cell-induced suppressive function of Treg cells. The anti-TNF-alpha reagent, etanercept, restored the functional activity and Foxp3 expression of CD4(+)CD25(high) Treg derived from allergic asthmatics. CONCLUSIONS: The functional insufficiency of nTreg cells in patients with allergic asthma may be related to the enhanced production of TNF-alpha and its effect on the Foxp3 expression. These results may explain, in part, the effectiveness of anti-TNF-alpha therapy in the treatment of allergic asthma.
Authors:
Y-L Lin; C-C Shieh; J-Y Wang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Allergy     Volume:  63     ISSN:  1398-9995     ISO Abbreviation:  Allergy     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2007-12-06     Completed Date:  2008-01-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7804028     Medline TA:  Allergy     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  67-74     Citation Subset:  IM    
Affiliation:
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD24 / genetics,  immunology*
Antigens, CD4 / genetics,  immunology*
Asthma / genetics,  immunology*
Case-Control Studies
Cell Proliferation / drug effects
Child
Child, Preschool
Down-Regulation
Enzyme-Linked Immunosorbent Assay
Female
Forkhead Transcription Factors / genetics,  immunology*,  metabolism
Gene Expression Regulation
Humans
Male
Probability
Sensitivity and Specificity
Statistics, Nonparametric
T-Lymphocytes, Regulatory / drug effects,  immunology*
Tumor Necrosis Factor-alpha / immunology*,  pharmacology
Chemical
Reg. No./Substance:
0/Antigens, CD24; 0/Antigens, CD4; 0/FOXP3 protein, human; 0/Forkhead Transcription Factors; 0/Tumor Necrosis Factor-alpha

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