Source:http://linkedlifedata.com/resource/pubmed/id/18424765
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
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| pubmed:dateCreated |
2008-4-21
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| pubmed:abstractText |
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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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
0022-1767
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
180
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
6411-20
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| pubmed:meshHeading |
pubmed-meshheading:18424765-Adult,
pubmed-meshheading:18424765-Antigens, CD,
pubmed-meshheading:18424765-Chronic Disease,
pubmed-meshheading:18424765-Disease Progression,
pubmed-meshheading:18424765-Female,
pubmed-meshheading:18424765-Homeostasis,
pubmed-meshheading:18424765-Humans,
pubmed-meshheading:18424765-Immunologic Memory,
pubmed-meshheading:18424765-Male,
pubmed-meshheading:18424765-Middle Aged,
pubmed-meshheading:18424765-Multiple Sclerosis,
pubmed-meshheading:18424765-Receptors, Antigen, T-Cell,
pubmed-meshheading:18424765-Recovery of Function,
pubmed-meshheading:18424765-T-Lymphocytes, Regulatory,
pubmed-meshheading:18424765-Thymus Gland,
pubmed-meshheading:18424765-Time Factors
|
| pubmed:year |
2008
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| pubmed:articleTitle |
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.
|
| pubmed:affiliation |
Hasselt University, Biomedisch Onderzoeksinstituut and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|