Secondary progressive in contrast to relapsing-remitting multiple sclerosis patients show a normal CD4+CD25+ regulatory T-cell function and FOXP3 expression.

Accumulating evidence indicates an immunosuppressive role for CD4(+)CD25(+) regulatory T cells (Tregs) in autoimmune diseases. Although an impaired Treg function in patients with relapsing-remitting multiple sclerosis (RR-MS) has been reported recently, no information is available so far about Treg function in the progressive stage of the disease. In the present study, the phenotypic and functional characteristics of CD4(+)CD25(+) T cells isolated from the peripheral blood of patients with RR-MS and secondary progressive multiple sclerosis (SP-MS) were investigated. No significant quantitative or phenotypic abnormalities in CD4(+)CD25(+) T cells from RR- and SP-MS patients were detected. However, whereas a reduced suppressor function of CD4(+)CD25(+) T cells toward proliferation and interferon-gamma production of CD4(+)CD25(-) responder T cells was found in RR-MS patients, SP-MS patients showed a normal Treg function. The suppressive capacity of MS-derived CD4(+)CD25(+) T cells was correlated with disease duration but not with age, indicating that Treg function is more affected in the early phase of the disease process. Consistently with the suppressive capacity, CD4(+)CD25(+) T cells from SP-MS patients showed normal levels of FOXP3 mRNA in contrast to RR-MS patients that had a reduced FOXP3 expression. These data are the first to demonstrate differences in function and FOXP3 expression of CD4(+)CD25(+) T cells from patients with RR- and SP-MS.

Venken K ，Hellings N ，Hensen K ，Rummens JL ，Medaer R ，D'hooghe MB ，Dubois B ，Raus J ，Stinissen P ... -  《JOURNAL OF NEUROSCIENCE RESEARCH》

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.

Venken K ，Hellings N ，Thewissen M ，Somers V ，Hensen K ，Rummens JL ，Medaer R ，Hupperts R ，Stinissen P ... -  《-》

Effect of IFN-beta therapy on the frequency and function of CD4(+)CD25(+) regulatory T cells and Foxp3 gene expression in relapsing-remitting multiple sclerosis (RRMS): a preliminary study.

Interferon-beta (IFN-beta) is an immunomodulatory drug of choice to control relapsing-remitting multiple sclerosis (RR-MS), although its function is still unclear. A reduced suppressive function of CD4(+)CD25(+) regulatory T cells (T(reg)) has been shown in RR-MS patients. In this study, to understand the effect of IFN-ss on CD4(+)CD25(+) regulatory T cells, we analyzed the frequency and function of these cells and Foxp3 gene expression before and after treatment. We evaluated the frequency and function of CD4(+)CD25(+)Foxp3(+) regulatory T cells by flow cytometry and co-culture inhibition test respectively and gene expression of Foxp3 by real-time PCR in a longitudinal follow-up study in 18 relapsing-remitting MS patients. Our data revealed that IFN-beta significantly improved frequency and suppressive function of T(reg) cells (P<0.05) without any significant effect on gene expression of Foxp3 after 6 months. The results of the present study indicate that IFN-beta therapy in some of patients with RR-MS may restore function of regulatory T cells and control the unchecked immune cascade activity. Larger longitudinal studies on more MS patients are required to confirm our findings.

Namdar A ，Nikbin B ，Ghabaee M ，Bayati A ，Izad M ... -  《-》

CD127 immunophenotyping suggests altered CD4+ T cell regulation in primary progressive multiple sclerosis.

McKay FC ，Swain LI ，Schibeci SD ，Rubio JP ，Kilpatrick TJ ，Heard RN ，Stewart GJ ，Booth DR ... -  《JOURNAL OF AUTOIMMUNITY》

CD39+Foxp3+ regulatory T Cells suppress pathogenic Th17 cells and are impaired in multiple sclerosis.

Fletcher JM ，Lonergan R ，Costelloe L ，Kinsella K ，Moran B ，O'Farrelly C ，Tubridy N ，Mills KH ... -  《-》