Document Detail

Glatiramer acetate-specific T cells in the brain express T helper 2/3 cytokines and brain-derived neurotrophic factor in situ.
MedLine Citation:
PMID:  14614135     Owner:  NLM     Status:  MEDLINE    
The ability of a remedy to modulate the pathological process in the target organ is crucial for its therapeutic activity. Glatiramer acetate (GA, Copaxone, Copolymer 1), a drug approved for the treatment of multiple sclerosis, induces regulatory T helper 2/3 cells that penetrate the CNS. Here we investigated whether these GA-specific T cells can function as suppressor cells with therapeutic potential in the target organ by in situ expression of T helper 2/3 cytokines and neurotrophic factors. GA-specific cells and their in situ expression were detected on the level of whole-brain tissue by using a two-stage double-labeling system: (i) labeling of the GA-specific T cells, followed by their adoptive transfer, and (ii) detection of the secreted factors in the brain by immunohistological methods. GA-specific T cells in the CNS demonstrated intense expression of the brain-derived neurotrophic factor and of two antiinflammatory cytokines, IL-10 and transforming growth factor beta. No expression of the inflammatory cytokine IFN-gamma was observed. This pattern of expression was manifested in brains of normal and experimental autoimmune encephalomyelitis-induced mice to which GA-specific cells were adoptively transferred, but not in control mice. Furthermore, infiltration of GA-induced cells to the brain resulted in bystander expression of IL-10 and transforming growth factor beta by resident astrocytes and microglia. The ability of infiltrating GA-specific cells to express antiinflammatory cytokines and neurotrophic factor in the organ in which the pathological processes occur correlates directly with the therapeutic activity of GA in experimental autoimmune encephalomyelitis/multiple sclerosis.
Rina Aharoni; Basak Kayhan; Raya Eilam; Michael Sela; Ruth Arnon
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-11-12
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  100     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2003-12-03     Completed Date:  2004-02-02     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  14157-62     Citation Subset:  IM    
Department of Immunology, The Weizmann Institute, Rehovot 76100, Israel.
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MeSH Terms
Adoptive Transfer
Brain / drug effects,  immunology*,  metabolism
Brain-Derived Neurotrophic Factor / metabolism*
Cytokines / metabolism*
Encephalomyelitis, Autoimmune, Experimental / drug therapy,  immunology,  metabolism
Immunosuppressive Agents / pharmacology*
Interferon-gamma / metabolism
Interleukin-10 / metabolism
Mice, Inbred BALB C
Multiple Sclerosis / drug therapy,  immunology,  metabolism
Peptides / pharmacology*
T-Lymphocyte Subsets / drug effects,  immunology,  metabolism
T-Lymphocytes, Helper-Inducer / drug effects*,  immunology*,  metabolism
Th2 Cells / drug effects,  immunology,  metabolism
Transforming Growth Factor beta / metabolism
Reg. No./Substance:
0/Brain-Derived Neurotrophic Factor; 0/Cytokines; 0/Immunosuppressive Agents; 0/Peptides; 0/Transforming Growth Factor beta; 0/copolymer 1; 130068-27-8/Interleukin-10; 82115-62-6/Interferon-gamma
Erratum In:
Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):12288

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

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