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- Title
Compromised CD4<sup>+</sup> CD25<sup>high</sup> 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, Robert; Hupperts, Raymond; Stinissen, Piet
- Abstract
CD4+ CD25high 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+ CD25high 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)-β-treated RR-MS patients showed restored numbers of FOXP3+ Tregs. Furthermore, a higher percentage of CD4+ CD25high 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+ CD25high 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.
- Subjects
CD antigens; T cells; MULTIPLE sclerosis; CELLULAR control mechanisms; IMMUNOSUPPRESSION; NERVOUS system abnormalities; PATIENTS
- Publication
Immunology, 2008, Vol 123, Issue 1, p79
- ISSN
0019-2805
- Publication type
Article
- DOI
10.1111/j.1365-2567.2007.02690.x