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.
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.
Venken
Koen
K
Hasselt University, Biomedisch Onderzoeksinstituut and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium.
Hellings
Niels
N
Thewissen
Marielle
M
Somers
Veerle
V
Hensen
Karen
K
Rummens
Jean-Luc
JL
Medaer
Robert
R
Hupperts
Raymond
R
Stinissen
Piet
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D005260:Female; D051858:Forkhead Transcription Factors / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D016130:Immunophenotyping; D016899:Interferon-beta / Q000627:therapeutic use; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016899:Interferon-beta