| Type 2 monocyte and microglia differentiation mediated by glatiramer acetate therapy in patients with multiple sclerosis. | |
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MedLine Citation:
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PMID: 15153538 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Ho Jin Kim; Igal Ifergan; Jack P Antel; Rosanne Seguin; Martin Duddy; Yves Lapierre; Farzaneh Jalili; Amit Bar-Or |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 172 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 2004 Jun |
Date Detail:
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Created Date: 2004-05-21 Completed Date: 2004-08-06 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 7144-53 Citation Subset: AIM; IM |
Affiliation:
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Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Antigen-Presenting Cells / cytology, drug effects Cell Differentiation / drug effects Female Humans Interferon-gamma / pharmacology Interleukin-10 / biosynthesis Interleukin-12 / biosynthesis Interleukin-5 / pharmacology Male Microglia / cytology, drug effects* Monocytes / cytology, drug effects* Multiple Sclerosis / drug therapy*, immunology Peptides / pharmacology, therapeutic use* Th1 Cells / cytology Th2 Cells / cytology |
| Chemical | |
Reg. No./Substance:
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0/Interleukin-5; 0/Peptides; 0/copolymer 1; 130068-27-8/Interleukin-10; 187348-17-0/Interleukin-12; 82115-62-6/Interferon-gamma |
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