scholarly journals Redox Imbalance in CD4+ T Cells of Relapsing-Remitting Multiple Sclerosis Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Mohammad Javad Tavassolifar ◽  
Abdorreza Naser Moghadasi ◽  
Behnaz Esmaeili ◽  
Omid Sadatpour ◽  
Mohammad Vodjgani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
T Cells ◽  
Cd4 T Cells ◽  
Gene Expression Level ◽  
Expression Level ◽  
Related Factor ◽  
Healthy Controls ◽  
Relapsing Remitting ◽  
Multiple Sclerosis Patients

As a prevalent autoimmune disease of the central nervous system in young adults, multiple sclerosis (MS) is mediated by T cells, particularly CD4+ subsets. Given the evidence that the perturbation in reactive oxygen species (ROS) production has a pivotal role in the onset and progression of MS, its regulation through the antioxidant molecules is too important. Here, we investigated the level of the redox system components in lymphocytes and CD4+ T cells of MS patients. The study was performed on relapsing-remitting MS (RRMS) patients ( n = 29 ) and age- and sex-matched healthy controls ( n = 15 ). Peripheral blood mononuclear cells (PBMCs) were cultured and stimulated by anti-CD3/CD28. The level of ROS, anion superoxide (O2-), and L-𝛾-glutamyl-Lcysteinylglycine (GSH) was measured by flow cytometry in lymphocytes/CD4+ T cells. The gene expression level of gp91phox, catalase, superoxide dismutase 1/2 (SOD), and nuclear factor-E2-related factor (Nrf2) was also measured by real-time PCR. We found that lymphocytes/CD4+ T cells of RRMS patients at the relapse phase significantly produced higher levels of ROS and O2- compared to patients at the remission phase ( P value < 0.001) and healthy controls ( P value < 0.001 and P value < 0.05, respectively). Interestingly, the gene expression level of gp91phox, known as the catalytic subunit of the NADPH oxidase, significantly increased in MS patients at the relapse phase ( P value < 0.05). Furthermore, the catalase expression augmented in patients at the acute phase ( P value < 0.05), while an increased expression of SOD1 and Nrf2 was found in RRMS patients at relapse and remission phases ( P value < 0.05). The increased production of ROS in CD4+ T cells of RRMS patients highlights the importance of amplifying antioxidant components as an efficient approach to ameliorate disease activity in MS patients.

CRYAB modulates the activation of CD4+ T cells from relapsing–remitting multiple sclerosis patients

2013 ◽  
Vol 19 (14) ◽  
pp. 1867-1877 ◽  
Author(s):  
Que Lan Quach ◽  
Luanne M Metz ◽  
Jenna C Thomas ◽  
Jonathan B Rothbard ◽  
Lawrence Steinman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Cytokine Production ◽  
Clinical Signs ◽  
Healthy Controls ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background: Suppression of activation of pathogenic CD4+ T cells is a potential therapeutic intervention in multiple sclerosis (MS). We previously showed that a small heat shock protein, CRYAB, reduced T cell proliferation, pro-inflammatory cytokine production and clinical signs of experimental allergic encephalomyelitis, a model of MS. Objective: We assessed whether the ability of CRYAB to reduce the activation of T cells translated to the human disease. Methods: CD4+ T cells from healthy controls and volunteers with MS were activated in vitro in the presence or absence of a CRYAB peptide (residues 73–92). Parameters of activation (proliferation rate, cytokine secretion) and tolerance (anergy, activation-induced cell death, microRNAs) were evaluated. Results: The secretion of pro-inflammatory cytokines by CD4+ T cells was decreased in the presence of CRYAB in a subset of relapsing–remitting multiple sclerosis (RRMS) participants with mild disease severity while no changes were observed in healthy controls. Further, there was a correlation for higher levels of miR181a microRNA, a marker upregulated in tolerant CD8+ T cells, in CD4+ T cells of MS patients that displayed suppressed cytokine production (responders). Conclusion: CRYAB may be capable of suppressing the activation of CD4+ T cells from a subset of RRMS patients who appear to have less disability but similar age and disease duration.

scholarly journals Quantitative Proteomics Reveals Protein Dysregulation During T Cell Activation in Multiple Sclerosis Patients Compared to Healthy Controls

2021 ◽  
Author(s):  
Chiara Cappelletti ◽  
Anna Maria Eriksson ◽  
Ina Skaara Brorson ◽  
Ingvild S. Leikfoss ◽  
Oda Glomstad Kråbøl ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Susceptibility Genes ◽  
Healthy Controls ◽  
Activated T Cells ◽  
Multiple Sclerosis Patients

Abstract Background: Multiple sclerosis (MS) is an autoimmune, neurodegenerative disorder with a strong genetic component that acts in a complex interaction with environmental factors for disease development. CD4 + T cells are pivotal players in MS pathogenesis, where peripherally activated T cells migrate to the central nervous system leading to demyelination and axonal degeneration. Through a proteomic approach, we aim at identifying dysregulated pathways in activated T cells from MS patients as compared to healthy controls. Methods: CD4 + T cells were purified from peripheral blood from MS patients and healthy controls by magnetic separation. Cells were left unstimulated or stimulated in vitro through the TCR and costimulatory CD28 receptor for 24 hours prior to sampling. Electrospray liquid chromatographytandem mass spectrometry was used to measure protein abundances. Results: Upon T cell activation the abundance of 1,801 proteins was changed. Among these proteins, we observed an enrichment of proteins expressed by MS-susceptibility genes. When comparing protein abundances in T cell samples from healthy controls and MS patients, 18 and 33 proteins were differentially expressed in unstimulated and stimulated CD4 + T cells, respectively. Moreover, 353 and 304 proteins were identified as proteins exclusively induced upon T cell activation in healthy controls and MS patients, respectively and dysregulation of the Nur77 pathway was observed only in samples from MS patients. Conclusions: Our study highlights the importance of CD4 + T cell activation for MS, as proteins that change in abundance upon T cell activation are enriched for proteins encoded by MS susceptibility genes. The results provide evidence for proteomic disturbances in T cell activation in MS, and pinpoint to dysregulation of the Nur77 pathway, a biological pathway known to limit aberrant effector T cell responses.

A time dependent gene expression level of C3, C3aR and CTSL in CD4+ T cells

Immunobiology ◽  
2016 ◽  
Vol 221 (10) ◽  
pp. 1201
Author(s):  
Cecilie Bo Hansen ◽  
Anton Willer ◽  
Hanne Vibeke Hansen Marquart ◽  
Martin Kolev ◽  
Claudia Kemper ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Cd4 T Cells ◽  
Time Dependent ◽  
Gene Expression Level ◽  
Expression Level

scholarly journals Altered Expression of miR-326 in T Cell-derived Exosomes of Patients with Relapsing-remitting Multiple Sclerosis

2019 ◽  
Author(s):  
Maryam Azimi ◽  
Mojdeh Ghabaee ◽  
Abdorreza Naser Moghadasi ◽  
Maryam Izad
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Cd4 T Cells ◽  
Pathological Condition ◽  
Healthy Controls ◽  
Altered Expression ◽  
Expression Levels ◽  
Relapsing Remitting ◽  
Th17 Differentiation ◽  
Relapsing Remitting Multiple Sclerosis

Invasion of auto-reactive CD4+ T cells especially Th17 into central nervous system (CNS) is an underlying pathogenic mechanism in multiple sclerosis (MS). CD4+ T cells release exosomes which are enriched in microRNAs, reflective of cell’s physiological or pathological condition. Thus exosomes could be potent agents to provide quantitative and qualitative information about involved cells in MS. We investigated the expression of pathogenic microRNAs in T cells-derived exosomes of MS patients or healthy controls. Conventional T cells (Tconv) derived from relapsing-remitting (RR) MS patients (n=10) and healthy controls (n=10) were purified and cultured for 3 days by soluble anti-CD3/CD28. Exosomes were purified from cultured-T cells supernatants. The expression levels of exosomal miR-146a, miR-29a, miR-155, and miR-326 were quantified by real-time PCR. A statistically significant increased expression of miR-326 in Tconv-derived exosomes was observed in RRMS patients as compared with controls (7.5±1.88vs 2.51±0.9 p=0.03), On the contrary, no differences were found in the expression levels of miR-155, miR-146a, and miR-29a, in Tconv-derived exosomes of  patients as compared with controls (p>0.05).  Our results point to altered expression in exosome-derived microRNAs. MiR-326 was previously shown to play a role in the immunopathogenesis of MS by inducing TH17 differentiation and maturation. Therefore, miR-326 containing exosomes might also be a potential clinical target in course of MS. Moreover, the deregulation of this miRNA in exosomes may serve as a diagnostic and prognostic biomarker.  

scholarly journals No differential gene expression for CD4+ T cells of MS patients and healthy controls

2019 ◽  
Vol 5 (2) ◽  
pp. 205521731985690 ◽  
Author(s):  
Ina S Brorson ◽  
Anna Eriksson ◽  
Ingvild S Leikfoss ◽  
Elisabeth G Celius ◽  
Pål Berg-Hansen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
T Cells ◽  
Differential Gene Expression ◽  
Genetic Variants ◽  
Healthy Controls ◽  
Expression Studies ◽  
Differential Gene ◽  
Gene Expression Studies ◽  
Multiple Sclerosis Patients

Background Multiple sclerosis-associated genetic variants indicate that the adaptive immune system plays an important role in the risk of developing multiple sclerosis. It is currently not well understood how these multiple sclerosis-associated genetic variants contribute to multiple sclerosis risk. CD4+ T cells are suggested to be involved in multiple sclerosis disease processes. Objective We aim to identify CD4+ T cell differential gene expression between multiple sclerosis patients and healthy controls in order to understand better the role of these cells in multiple sclerosis. Methods We applied RNA sequencing on CD4+ T cells from multiple sclerosis patients and healthy controls. Results We did not identify significantly differentially expressed genes in CD4+ T cells from multiple sclerosis patients. Furthermore, pathway analyses did not identify enrichment for specific pathways in multiple sclerosis. When we investigated genes near multiple sclerosis-associated genetic variants, we did not observe significant enrichment of differentially expressed genes. Conclusion We conclude that CD4+ T cells from multiple sclerosis patients do not show significant differential gene expression. Therefore, gene expression studies of all circulating CD4+ T cells may not result in viable biomarkers. Gene expression studies of more specific subsets of CD4+ T cells remain justified to understand better which CD4+ T cell subsets contribute to multiple sclerosis pathology.

The Feature of TCR Zeta Gene in CD4+ and CD8+ T Cells in Patients with CML.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4526-4526
Author(s):  
Si Chen ◽  
Yangqiu Li ◽  
Shaohua Chen ◽  
Lijian Yang ◽  
Xiuli Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Gene Expression Level ◽  
Expression Level ◽  
Chain Gene ◽  
Zeta Chain ◽  
Normal Individuals ◽  
Normal Controls

Abstract The T-cell receptor (TCR) zeta chain is a master sensor and regulator of lymphocyte responses which plays a critical role in TCR-mediated signal transduction. The abnormal expression of TCR zeta gene was found in some malignancies and immune disease. Cellular immune deficiency is the common feature in patients with chronic myeloid leukemia (CML). Our previous studies had showed that 60% of CML patients displayed an abnormally low expression of TCR zeta chain in peripheral blood mononuclear cells (PBMCs). To further estimate the changes of zeta chain expression of T-lymphocyte subsets in CML, TCR zeta chain gene expression level in purified CD4+ and CD8+ T cells sorted by MACS were detected by real-Time PCR with SYBR Green I technique, CD4+ and CD8+ T cells from both 10 cases with CML and 10 normal individuals were selected to analyze in the study. β2 -microglobulin was used as an endogenous reference. Relative changes in TCR zeta gene expression level were used by the 2−ΔCt×100% method. The relative mRNA expression level of TCR zeta gene in CD4+ and CD8+ T cells from CML was 4.06±4.82% and 3.82±4.25% respectively, whereas 7.75±2.52% and 5.19±1.25% were found in normal individuals. There was a wide range in the TCR zeta gene expression level of CD4+ T cells from CML patients (0.23–15.93%,) with a median value of 1.77%, whereas the a range of (4.74–12.81%) with a median of 7.93% was showed in normal controls (P=0.046). The expression level of TCR zeta gene in CD8+ T cells from controls ranged from 3.47% to 6.75% (median 5.52%) and in CML patients from 0.86% to 15.55% with a median of 2.51% (P=0.340). The results indicated that, compared with normal controls, zeta chain gene expression was obviously down-regulated in CD4+ T cells from patients with CML. However, there was not significant different in expression level of TCR zeta gene of CD8+ T cells between CML patients and normal individuals. Moreover, the expression level of TCR zeta gene is nonsignificant age-associated or gender-link in CD4+ T cells and CD8+ T cells from patients with CML. In conclusions, the results provide at first the difference of TCR-zeta gene expression pattern in CD4+ and CD8+ T cells from patients with CML, this may be reflective of signaling difference between the different T cell subtypes in immunodeficiency state of patients.

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