Document Detail

Type 2 monocyte and microglia differentiation mediated by glatiramer acetate therapy in patients with multiple sclerosis.
MedLine Citation:
PMID:  15153538     Owner:  NLM     Status:  MEDLINE    
Glatiramer acetate (GA) therapy of patients with multiple sclerosis (MS) represents a unique setting in which in vivo Th2 deviation of T cells is consistently observed and associated with clinical benefit in a human autoimmune disease. We postulated that APCs are important targets of GA therapy and demonstrate that treatment of MS patients with GA reciprocally regulates the IL-10/IL-12 cytokine network of monocytes in vivo. We further show that Th1- or Th2-polarized GA-reactive T cells isolated from untreated or treated MS patients mediate type 1 and 2 APC differentiation of human monocytes, based on their ability to efficiently induce subsequent Th1 and Th2 deviation of naive T cells, respectively. These observations are extended to human microglia, providing the first demonstration of type 2 differentiation of CNS-derived APCs. Finally, we confirm that the fundamental capacity of polarized T cells to reciprocally modulate APC function is not restricted to GA-reactive T cells, thereby defining a novel and dynamic positive feedback loop between human T cell and APC responses. In the context of MS, we propose that GA therapy results in the generation of type 2 APCs, contributing to Th2 deviation both in the periphery and in the CNS of MS patients. In addition to extending insights into the therapeutic mode of action of GA, our findings revisit the concept of bystander suppression and underscore the potential of APCs as attractive targets for therapeutic immune modulation.
Ho Jin Kim; Igal Ifergan; Jack P Antel; Rosanne Seguin; Martin Duddy; Yves Lapierre; Farzaneh Jalili; Amit Bar-Or
Related Documents :
8081518 - The immunology of multiple sclerosis: new intricacies and new insights.
16797728 - Effects of ifn-beta, leptin and simvastatin on lif secretion by t lymphocytes of ms pat...
7424968 - Pure red cell aplasia and the syndrome of multiple endocrine gland insufficiency.
18550828 - Orphan nuclear receptor nr4a2 expressed in t cells from multiple sclerosis mediates pro...
11222498 - Il-4 gene expression up-regulated by mercury in rat mast cells: a role of oxidant stres...
16714548 - Role for dendritic cells in immunoregulation during experimental vaginal candidiasis.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  172     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2004 Jun 
Date Detail:
Created Date:  2004-05-21     Completed Date:  2004-08-06     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7144-53     Citation Subset:  AIM; IM    
Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Antigen-Presenting Cells / cytology,  drug effects
Cell Differentiation / drug effects
Interferon-gamma / pharmacology
Interleukin-10 / biosynthesis
Interleukin-12 / biosynthesis
Interleukin-5 / pharmacology
Microglia / cytology,  drug effects*
Monocytes / cytology,  drug effects*
Multiple Sclerosis / drug therapy*,  immunology
Peptides / pharmacology,  therapeutic use*
Th1 Cells / cytology
Th2 Cells / cytology
Reg. No./Substance:
0/Interleukin-5; 0/Peptides; 0/copolymer 1; 130068-27-8/Interleukin-10; 187348-17-0/Interleukin-12; 82115-62-6/Interferon-gamma

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

Previous Document:  Stroma cell-derived factor 1alpha mediates desensitization of human neutrophil respiratory burst in ...
Next Document:  Topical glucocorticoid therapy directly induces up-regulation of functional CXCR4 on primed T lympho...