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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/8444

Title: Natural naive CD4(+)CD25(+)CD127(low) regulatory T cell (Treg) development and function are disturbed in multiple sclerosis patients: Recovery of memory treg homeostasis during disease progression
Authors: VENKEN, Koen
Hensen, K.
Issue Date: 2008
Citation: JOURNAL OF IMMUNOLOGY, 180(9). p. 6411-6420
Abstract: 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.
Notes: Hasselt Univ, Biomed Onderzoeksinst, B-3590 Diepenbeek, Belgium. Transnatl Univ Limburg, Sch Life Sci, Diepenbeek, Belgium. Univ Coll Prov Limburg, Dept Hlth Care, Rehabil & Hlth Care Res Ctr, Hasselt, Belgium. Virga Jasse Hosp, Clin Lab Expt Hematol, Hasselt, Belgium.
URI: http://hdl.handle.net/1942/8444
Link to publication: http://www.jimmunol.org/cgi/content/abstract/180/9/6411
ISI #: 000257507000077
ISSN: 0022-1767
Category: A1
Type: Journal Contribution
Validation: ecoom, 2009
Appears in Collections: Research publications

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