Document Detail

Oligoclonal myelin-reactive T-cell infiltrates derived from multiple sclerosis lesions are enriched in Th17 cells.
MedLine Citation:
PMID:  18977698     Owner:  NLM     Status:  MEDLINE    
In this study, acute and chronic brain and spinal cord lesions, and normal appearing white matter (NAWM), were resected post-mortem from a patient with aggressive relapsing-remitting multiple sclerosis (MS). T-cell infiltrates from the central nervous system (CNS) lesions and NAWM were separated and characterized in-vitro. All infiltrates showed a proliferative response against multiple myelin peptides. Studies of the T-cell receptor (TCR)Vbeta and Jbeta usage revealed a very skewed repertoire with shared complementarity-determining region (CDR)3 lengths detected in all CNS lesions and NAWM. In the acute lesion, genomic profiling of the infiltrating T-cells revealed up-regulated expression of TCRalpha and beta chain, retinoic acid-related orphan nuclear hormone receptor C (RORC) transcription factor, and multiple cytokine genes that mediate Th17 cell expansion. The differentially expressed genes involved in regulation of Th17 cells represent promising targets for new therapies of relapsing-remitting MS.
Monica Montes; Xin Zhang; Laureline Berthelot; David-Axel Laplaud; Sophie Brouard; Jianping Jin; Sarah Rogan; Diane Armao; Valerie Jewells; Jean-Paul Soulillou; Silva Markovic-Plese
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-11-05
Journal Detail:
Title:  Clinical immunology (Orlando, Fla.)     Volume:  130     ISSN:  1521-7035     ISO Abbreviation:  Clin. Immunol.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-05     Completed Date:  2009-01-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100883537     Medline TA:  Clin Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  133-44     Citation Subset:  IM    
Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
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MeSH Terms
Central Nervous System / immunology,  pathology
Gene Expression Profiling
Interleukin-17 / genetics,  immunology*
Multiple Sclerosis, Relapsing-Remitting / genetics,  immunology*,  pathology
Myelin Sheath / immunology*,  metabolism
Receptors, Antigen, T-Cell, alpha-beta / immunology,  metabolism
Receptors, Cytokine / genetics,  immunology
T-Lymphocyte Subsets / immunology*,  metabolism
T-Lymphocytes, Helper-Inducer / immunology*,  metabolism
Transcription Factors / genetics,  immunology
Grant Support
Reg. No./Substance:
0/Interleukin-17; 0/Receptors, Antigen, T-Cell, alpha-beta; 0/Receptors, Cytokine; 0/Transcription Factors

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