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Glucocorticoids increase CD4CD25 cell percentage and Foxp3 expression in patients with multiple sclerosis.

ABSTRACT: To determine whether percentages of CD4(+)CD25(high) T cells (a group of regulatory T cells, Treg) differ in patients with multiple sclerosis (MS) in relapse vs remission after glucocorticoid treatment and whether treatment for relapses changes Treg population and the expression of Foxp3, a key Treg-associated molecule.Peripheral blood mononuclear cells (PBMC) were obtained from 20 patients with MS during relapse, just before and 2 days after starting steroid treatment (i.v. methylprednisolone 1 g/day for 3 days) and then 6 weeks after treatment. CD4(+)CD25(hi) cells were analysed by using flow cytometry. Cytokines were measured by using an ELISA and Foxp3, CD3 and CD25 expression by using quantitative real-time PCR.The percentage of CD4(+)CD25(hi) cells, plasma IL-10 and Foxp3/CD3 ratio increased 48 h after methylprednisolone initiation and returned to baseline values by 6 weeks post-treatment.Results suggest that glucocorticoids increase Treg cell functional molecules and percentages. This may be a mechanism whereby steroids expedite recovery from MS relapses.

SUBMITTER: Braitch M

PROVIDER: S-EPMC4467559 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Glucocorticoids increase CD4CD25 cell percentage and Foxp3 expression in patients with multiple sclerosis.

Braitch M M Harikrishnan S S Robins R A RA Nichols C C Fahey A J AJ Showe L L Constantinescu C S CS

Acta neurologica Scandinavica 20090401 4

<h4>Objectives</h4>To determine whether percentages of CD4(+)CD25(high) T cells (a group of regulatory T cells, Treg) differ in patients with multiple sclerosis (MS) in relapse vs remission after glucocorticoid treatment and whether treatment for relapses changes Treg population and the expression of Foxp3, a key Treg-associated molecule.<h4>Materials and methods</h4>Peripheral blood mononuclear cells (PBMC) were obtained from 20 patients with MS during relapse, just before and 2 days after star ...[more]

PMID: 18771523

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Project description:BackgroundMagnetic Resonance Imaging (MRI) is an established tool in diagnosing and evaluating disease activity in Multiple Sclerosis (MS). While clinical-radiological correlations are limited in general, hypointense T1 lesions (also known as Black Holes (BH)) have shown some promising results. The definition of BHs is very heterogeneous and depends on subjective visual evaluation.ObjectiveWe aimed to improve clinical-radiological correlations by defining BHs using T1 relaxation time (T1-RT) thresholds to achieve best possible correlation between BH lesion volume and clinical disability.Method40 patients with mainly relapsing-remitting MS underwent MRI including 3-dimensional fluid attenuated inversion recovery (FLAIR), magnetization-prepared rapid gradient echo (MPRAGE) before and after Gadolinium (GD) injection and double inversion-contrast magnetization-prepared rapid gradient echo (MP2RAGE) sequences. BHs (BHvis) were marked by two raters on native T1-weighted (T1w)-MPRAGE, contrast-enhancing lesions (CE lesions) on T1w-MPRAGE after GD and FLAIR lesions (total-FLAIR lesions) were detected separately. BHvis and total-FLAIR lesion maps were registered to MP2RAGE images, and the mean T1-RT were calculated for all lesion ROIs. Mean T1 values of the cortex (CTX) were calculated for each patient. Subsequently, Spearman rank correlations between clinical scores (Expanded Disability Status Scale and Multiple Sclerosis Functional Composite) and lesion volume were determined for different T1-RT thresholds.ResultsSignificant differences in T1-RT were obtained between all different lesion types with highest T1 values in visually marked BHs (BHvis: 1453.3±213.4 ms, total-FLAIR lesions: 1394.33±187.38 ms, CTX: 1305.6±35.8 ms; p<0.05). Significant correlations between BHvis/total-FLAIR lesion volume and clinical disability were obtained for a wide range of T1-RT thresholds. The highest correlation for BHvis and total-FLAIR lesion masks were found at T1-RT>1500 ms (Expanded Disability Status Scale vs. lesion volume: rBHvis = 0.442 and rtotal-FLAIR = 0.497, p<0.05; Multiple Sclerosis Functional Composite vs. lesion volume: rBHvis = -0.53 and rtotal-FLAIR = -0.627, p<0.05).ConclusionClinical-radiological correlations in MS patients are increased by application of T1-RT thresholds. With the short acquisition time of the MP2RAGE sequences, quantitative T1 maps could be easily established in clinical studies.

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Glucocorticoids increase CD4CD25 cell percentage and Foxp3 expression in patients with multiple sclerosis.

Publications

Glucocorticoids increase CD4CD25 cell percentage and Foxp3 expression in patients with multiple sclerosis.

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