Document Detail


FOXP3, CBLB and ITCH gene expression and cytotoxic T lymphocyte antigen 4 expression on CD4(+) CD25(high) T cells in multiple sclerosis.
MedLine Citation:
PMID:  23039885     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Expression of the forkhead box protein 3 (FoxP3) transcription factor is regulated by the E3 ubiquitin ligases Itch and Cbl-b and induces regulatory activity CD4(+) CD25(high) T cells. Treatment with interferon (IFN)-β enhances regulatory T cell activity in multiple sclerosis (MS). We studied the phenotype of CD4(+) CD25(high) T cells in MS by flow cytometry and its relationship with expression of the FOXP3, ITCH and CBLB genes. We found that untreated MS patients had lower cell surface expression of cytotoxic T lymphocyte antigen 4 (CTLA-4) on CD4(+) CD25(high) T cells and higher intracellular CTLA-4 expression than healthy controls. Cell surface expression of CTLA-4 on CD4(+) CD25(high) T cells correlated with expression of FOXP3 mRNA in untreated patients and increased significantly with time from most recent injection in patients treated with IFN-β. FOXP3 mRNA expression correlated with CBLB and ITCH and T helper type 2 cytokine mRNA expression in MS patients. These data link expression of FOXP3, CBLB and ITCH mRNA and CTLA-4 expression on the surface of CD4(+) CD25(high) T cell in MS. We hypothesize that this may reflect alterations in the inhibitory effect of CTLA-4 or in regulatory T cell function.
Authors:
F Sellebjerg; M Krakauer; M Khademi; T Olsson; P S Sørensen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and experimental immunology     Volume:  170     ISSN:  1365-2249     ISO Abbreviation:  Clin. Exp. Immunol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-08     Completed Date:  2013-03-18     Revised Date:  2013-11-05    
Medline Journal Info:
Nlm Unique ID:  0057202     Medline TA:  Clin Exp Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  149-55     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors Clinical and Experimental Immunology © 2012 British Society for Immunology.
Affiliation:
Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. sellebjerg@dadlnet.dk
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing / biosynthesis,  genetics*,  immunology
Adult
CD4-Positive T-Lymphocytes / immunology*
CTLA-4 Antigen / biosynthesis,  genetics*,  immunology
Female
Forkhead Transcription Factors / biosynthesis,  genetics*,  immunology
Gene Expression / immunology
Humans
Interferon-beta / biosynthesis,  genetics,  immunology
Interleukin-2 Receptor alpha Subunit / biosynthesis,  genetics*,  immunology
Male
Multiple Sclerosis / genetics*,  immunology
Proto-Oncogene Proteins c-cbl / biosynthesis,  genetics*,  immunology
RNA, Messenger / genetics,  immunology
Repressor Proteins / biosynthesis,  genetics*,  immunology
Ubiquitin-Protein Ligases / biosynthesis,  genetics*,  immunology
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/CTLA-4 Antigen; 0/CTLA4 protein, human; 0/FOXP3 protein, human; 0/Forkhead Transcription Factors; 0/IL2RA protein, human; 0/Interleukin-2 Receptor alpha Subunit; 0/RNA, Messenger; 0/Repressor Proteins; 77238-31-4/Interferon-beta; EC 6.3.2.-/Proto-Oncogene Proteins c-cbl; EC 6.3.2.19/CBLB protein, human; EC 6.3.2.19/ITCH protein, human; EC 6.3.2.19/Ubiquitin-Protein Ligases
Comments/Corrections

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