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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/7787

Title: Compromised CD4(+) CD25(high) regulatory T-cell function in patients with relapsing-remitting multiple sclerosis is correlated with a reduced frequency of FOXP3-positive cells and reduced FOXP3 expression at the single-cell level
Authors: VENKEN, Koen
HELLINGS, Niels
THEWISSEN, Marielle
SOMERS, Veerle
HENSEN, Karen
RUMMENS, Jean-Luc
MEDAER, Rob
Hupperts, Raymond
STINISSEN, Piet
Issue Date: 2008
Publisher: BLACKWELL PUBLISHING
Citation: IMMUNOLOGY, 123(1). p. 79-89
Abstract: CD4(+) CD25(high) regulatory T cells (Tregs) of patients with relapsing-remitting (RR) multiple sclerosis (MS), in contrast to those of patients with secondary progressive (SP) MS, show a reduced suppressive function. In this study, we analysed forkhead box P3 (FOXP3) at the single-cell level in MS patients and controls (healthy individuals and patients with other neurological diseases) by means of intracellular flow cytometry. Our data revealed a reduced number of peripheral blood CD4(+) CD25(high) FOXP3(+) T cells and lower FOXP3 protein expression per cell in RR-MS patients than in SP-MS patients and control individuals, which was correlated with the suppressive capacity of Tregs in these patients. Interestingly, interferon (IFN)-beta-treated RR-MS patients showed restored numbers of FOXP3(+) Tregs. Furthermore, a higher percentage of CD4(+) CD25(high) FOXP3(+) Tregs in RR-MS patients, as compared with controls and SP-MS patients, expressed CD103 and CD49d, adhesion molecules involved in T-cell recruitment towards inflamed tissues. This was consistent with a significantly increased number of CD27(+) CD25(high) CD4(+) T cells in the cerebrospinal fluid (CSF), as compared with peripheral blood, in RR-MS patients. Taken together, these data show aberrant FOXP3 expression at the single-cell level correlated with Treg dysfunction in RR-MS patients. Our results also suggest that Tregs accumulate in the CSF of RR-MS patients, in an attempt to down-regulate local inflammation in the central nervous system.
Notes: Hasselt Univ, Biomed Onderzoeksinst, B-3590 Diepenbeek, Belgium. Transnatl Univ Limburg, Sch Life Sci, Diepenbeek, Belgium. Virga Jesse Hosp, Clin Lab Expt Hematol, Hasselt, Belgium. Univ Hosp Maastricht, Dept Neurol, Maastricht, Netherlands.Stinissen, P, Hasselt Univ, Biomed Onderzoeksinst, Agoralaan Bldg A, B-3590 Diepenbeek, Belgium.piet.stinissen@uhasselt.be
URI: http://hdl.handle.net/1942/7787
DOI: 10.1111/j.1365-2567.2007.02690.x
ISI #: 000251586500014
ISSN: 0019-2805
Category: A1
Type: Journal Contribution
Validation: ecoom, 2009
Appears in Collections: Research publications

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