| Natural naive CD4+CD25+CD127low regulatory T cell (Treg) development and function are disturbed in multiple sclerosis patients: recovery of memory Treg homeostasis during disease progression. | |
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MedLine Citation:
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PMID: 18424765 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Patients with relapsing-remitting multiple sclerosis (RR-MS) show a suboptimal CD4(+)CD25(+) regulatory T cell (Treg) function, whereas no Treg alterations are observed in secondary progressive MS (SP-MS) patients. To clarify the difference in Treg activity between early and chronic disease stages in MS, we analyzed the functional capacity and homeostatic parameters of naive CD4(+)CD25(+)CD127(low)CD45RA(+) Tregs (nTregs) and their memory counterparts CD4(+)CD25(+)CD127(low)CD45RO(+) Tregs (mTregs) in untreated MS patients and healthy controls. Interestingly, whereas the suppressive capacity of FACS-sorted nTregs was impaired in both early and chronic MS patients, only the latter group showed a restored mTreg function. Consistent with this observation, chronic MS patients had increased numbers of mTregs as compared with age-matched early MS patients, whereas nTreg frequencies did not differ significantly. TCR excision circle numbers were reduced in nTregs of early MS patients, suggestive of a diminished nTreg thymic output. Moreover, a decreased number of CD31(+) mTregs were observed in early vs chronic MS patients, indicating that inflammatory processes drive the homeostatic turnover of mTregs during the early disease stage. Additionally, early MS patients showed a more restricted nTreg and mTreg TCR BV gene profile as compared with healthy controls and chronic MS patients. Finally, analysis of IFN-beta and glatiramer acetate-treated MS patients showed that these immunomodulatory drugs modify nTreg homeostasis. Taken together, this study provides strong evidence for a disturbed thymic nTreg development and function in MS patients. Moreover, memory Treg but not naive Treg homeostasis recovers during disease progression. |
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Authors:
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Koen Venken; Niels Hellings; Tom Broekmans; Karen Hensen; Jean-Luc Rummens; Piet Stinissen |
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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: 180 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 2008 May |
Date Detail:
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Created Date: 2008-04-21 Completed Date: 2008-06-04 Revised Date: - |
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: 6411-20 Citation Subset: AIM; IM |
Affiliation:
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Hasselt University, Biomedisch Onderzoeksinstituut and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Antigens, CD / immunology Chronic Disease Disease Progression Female Homeostasis / immunology* Humans Immunologic Memory* Male Middle Aged Multiple Sclerosis / immunology*, pathology Receptors, Antigen, T-Cell / immunology Recovery of Function / immunology* T-Lymphocytes, Regulatory / immunology*, pathology Thymus Gland / immunology*, pathology Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/Receptors, Antigen, T-Cell |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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