Document Detail


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.
MedLine Citation:
PMID:  18424765     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Koen Venken; Niels Hellings; Tom Broekmans; Karen Hensen; Jean-Luc Rummens; Piet Stinissen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  180     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-04-21     Completed Date:  2008-06-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6411-20     Citation Subset:  AIM; IM    
Affiliation:
Hasselt University, Biomedisch Onderzoeksinstituut and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium.
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MeSH Terms
Descriptor/Qualifier:
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:
0/Antigens, CD; 0/Receptors, Antigen, T-Cell

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