T Regulatory Cells Are Markers of Disease Activity in Multiple Sclerosis Patients (original) (raw)
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Immunology, 2008
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.
CD8+Foxp3+ T cells in peripheral blood of relapsing-remitting multiple sclerosis patients
Human Immunology, 2010
A defect of CD4 ϩ regulatory T cells (Treg) seems to be involved in the pathogenesis of multiple sclerosis (MS). Besides Treg, CD8 ϩ T cells also can suppress the immune response. Forkhead box p3 (Foxp3) is known to program the acquisition of suppressive capacities in CD4 ϩ T cells and recent studies showed that in vitro antigen activation leads to Foxp3 expression in CD8 ϩ T cells, gaining of suppressive activity. By flow cytometry we found a lower percentage of circulating CD8 ϩ Foxp3 ϩ T cells in relapsing than in remitting patients with MS and in controls. No significant differences were observed in CD8 ϩ Foxp3 ϩ T cell percentage between healthy subjects and patients in remission. Our data suggest that peripheral CD8 ϩ Foxp3 ϩ T cells may play a role in the maintenance of tolerance in MS. ᭧
Numerical status of CD4(+)CD25(+)FoxP3(+) and CD8(+)CD28(-) regulatory T cells in multiple sclerosis
Iranian journal of basic medical sciences, 2014
Regulatory T cells, including CD4+CD25+Fox3+ and CD8+CD28- cells play an important role in regulating the balance between immunity and tolerance. Since multiple sclerosis is an inflammatory autoimmune disease, regulatory T cells are considered to be involved in its pathogenesis. In this study, we investigated the circulatory numbers of the two mentioned types of regulatory T cells and also their association with different clinical characteristics in 84 multiple sclerosis patients. 84 patients with multiple sclerosis and 75 normal individuals were studied. Demographic and clinical information of all participants were collected via questionnaire and clinical examination as well as MRI. The peripheral blood frequency of two different subgroups of regulatory T cells (CD4+ CD25+Foxp3+ and CD8+CD28- cells) were analyzed by flow cytometry using anti-human antibodies conjugated with CD4-FITC / CD25-PE/Foxp3-PE-Cy5, CD3-PE/CD8a-PE-Cy5/CD28-FITC. The frequency of CD4+CD25+Foxp3+ cells in mult...
Decreased FOXP3 levels in multiple sclerosis patients
Journal of Neuroscience Research, 2005
Autoimmune diseases such as multiple sclerosis (MS) may result from the failure of tolerance mechanisms to prevent expansion of pathogenic T cells. Our study is the first to establish that MS patients have abnormalities in FOXP3 message and protein expression levels in peripheral CD4 þ CD25 þ T cells (Tregs) that are quantitatively related to a reduction in functional suppression induced during suboptimal T-cell receptor (TCR) ligation. Of importance, this observation links a defect in functional peripheral immunoregulation to an established genetic marker that has been unequivocally shown to be involved in maintaining immune tolerance and preventing autoimmune diseases. Diminished FOXP3 levels thus indicate impaired immunoregulation by Tregs that may contribute to MS. Future studies will evaluate the effects of therapies known to influence Treg cell function and FOXP3 expression, including TCR peptide vaccination and supplemental estrogen. V V C 2005 Wiley-Liss, Inc.
Regulatory T-cells (Tregs) are vital for maintaining immunological self-tolerance, and the transcription factor FOXP3 is considered critical for their development and function. Peripheral Treg induction may significantly contribute to the total Treg pool in healthy adults, and this pathway may be enhanced in thymic-deficient conditions like multiple sclerosis (MS). Here, we evaluated iTreg formation from memory versus naïve CD4 + CD25 − T-cell precursors. We report the novel finding that memory T-cells readily expressed CD25 and FOXP3, and demonstrated significantly greater suppressive function. Additionally, the CD25 − FOXP3 − fraction of stimulated memory T-cells also displayed robust suppression not observed in naïve counterparts or ex vivo resting (CD25 −) T-cells. This regulatory population was present in both healthy subjects and clinically-quiescent MS patients, but was specifically deficient during disease exacerbation. These studies indicate that iTreg development and function are precursor dependent. Furthermore, MS quiescence appears to correlate with restoration of suppressive function in memory-derived CD4 + CD25 − FOXP3 − iTregs.
Role of Regulatory T Cells in Pathogenesis and Biological Therapy of Multiple Sclerosis
Mediators of Inflammation, 2013
Multiple sclerosis (MS) is an inflammatory disease in which the myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms. It is caused by an autoimmune response to self-antigens in a genetically susceptible individual induced by unknown environmental factors. Principal cells of the immune system that drive the immunopathological processes are T cells, especially of TH1 and TH17 subsets. However, in recent years, it was disclosed that regulatory T cells took part in, too. Subsequently, there was endeavour to develop ways how to re-establish their physiological functions. In this review, we describe known mechanisms of action, efficacy, and side-effects of contemporary and emerging MS immunotherapeutical agents on Treg cells and other cells of the immune system involved in the immunopathogenesis of the disease. Furthermore, we discuss how laboratory immunology can offer physicians ...
FoxP3 isoforms and PD-1 expression by T regulatory cells in multiple sclerosis
Scientific reports, 2018
Forkhead box P3 (FoxP3)+ regulatory T cells (Treg) are powerful mediators of immune regulation and immune homeostasis. In humans, Tregs are a heterogeneous population expressing surface markers which define phenotypically and functionally distinct subsets. Moreover, it is now clear that intracellular staining for FoxP3 does not unequivocally identify "true" suppressor cells, since several FoxP3 isoforms exist, and different reagents for FoxP3 detection are available. Here, we propose a strategy to identify potentially functional and suppressive Treg cells in an autoimmune disease like multiple sclerosis, and we suggest that in patients affected by this disease these cells are both reduced in number and functionally exhausted.