scholarly journals Extracellular vesicle fibrinogen induces encephalitogenic CD8+ T cells in a mouse model of multiple sclerosis

2019 ◽  
Vol 116 (21) ◽  
pp. 10488-10493 ◽  
Author(s):  
Cory M. Willis ◽  
Alexandra M. Nicaise ◽  
Antoine Menoret ◽  
Jae Kyu Ryu ◽  
Andrew S. Mendiola ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Mouse Model ◽  
Cd8 T Cells ◽  
Extracellular Vesicle ◽  
Disease Phenotype ◽  
Experimental Autoimmune Encephalomyelitis Mouse ◽  
Relapsing Remitting ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Extracellular vesicles (EVs) are emerging as potent mediators of intercellular communication with roles in inflammation and disease. In this study, we examined the role of EVs from blood plasma (pEVs) in an experimental autoimmune encephalomyelitis mouse model of central nervous system demyelination. We determined that pEVs induced a spontaneous relapsing−remitting disease phenotype in MOG35–55-immunized C57BL/6 mice. This modified disease phenotype was found to be driven by CD8+ T cells and required fibrinogen in pEVs. Analysis of pEVs from relapsing−remitting multiple sclerosis patients also identified fibrinogen as a significant portion of pEV cargo. Together, these data suggest that fibrinogen in pEVs contributes to the perpetuation of neuroinflammation and relapses in disease.

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.

CD8+Foxp3+ T cells in peripheral blood of relapsing-remitting multiple sclerosis patients

2010 ◽  
Vol 71 (5) ◽  
pp. 437-441 ◽  
Author(s):  
Giovanni Frisullo ◽  
Viviana Nociti ◽  
Raffaele Iorio ◽  
Domenico Plantone ◽  
A. Katia Patanella ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Peripheral Blood ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Immunoglobulin-like transcript 3, an inhibitor of T cell activation, is reduced on blood monocytes during multiple sclerosis relapses and is induced by interferon β-1b

2009 ◽  
Vol 16 (1) ◽  
pp. 30-38 ◽  
Author(s):  
Mark A Jensen ◽  
Rachel N Yanowitch ◽  
Anthony T Reder ◽  
David M White ◽  
Barry GW Arnason
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Mononuclear Cells ◽  
Interferon Β ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Immunoglobulin-like transcripts (ILTs) are immunoregulatory proteins that either activate or inhibit immune responses. ILT3 is inhibitory and is expressed preferentially by antigen-presenting cells. When its extracellular domain binds to an unidentified ligand of activated T cells, the T cell is silenced. Our objective was to study the expression of ILT3 on circulating monocytes in RRMS. Freshly isolated peripheral blood mononuclear cells were analyzed by multicolored flow cytometry. The proportion of ILT3+CD14+ monocytes in blood, and ILT3 levels expressed by them, is lower in untreated multiple sclerosis in relapse than in: (1) untreated multiple sclerosis in remission (p < 0.009); (2) stable interferon β-treated relapsing—remitting multiple sclerosis (p < 0.001) and; (3) healthy controls (p < 0.009). Glatiramer acetate-stimulated CD4 + T cells, co-cultured with freshly isolated monocytes, proliferate significantly better (p = 0.0017 for multiple sclerosis; p = 0.0015 for controls) when T cell interaction with monocyte-expressed ILT3 is blocked by anti-ILT3 antibody. Interferon β is beneficial in multiple sclerosis; why so remains unclear. Interferon β-1b markedly increases ILT3 expression in vitro by monocytes from multiple sclerosis patients and controls. These findings identify a putative novel mechanism for the therapeutic benefit bestowed by Interferon β and a new target for therapeutic intervention in relapsing—remitting multiple sclerosis.

Frequency of circulating autoreactive T cells committed to myelin determinants in relapsing–remitting multiple sclerosis patients

2012 ◽  
Vol 144 (2) ◽  
pp. 117-126 ◽  
Author(s):  
Annie Elong Ngono ◽  
Ségolène Pettré ◽  
Marion Salou ◽  
Bouchaib Bahbouhi ◽  
Jean-Paul Soulillou ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Autoreactive T Cells ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Selective suppression of chemokine receptor CXCR3 expression by interferon-b1a in multiple sclerosis

2002 ◽  
Vol 8 (2) ◽  
pp. 104-107 ◽  
Author(s):  
T L Sørensen ◽  
F Sellebjerg
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Cerebrospinal Fluid ◽  
Chemokine Receptor ◽  
Cd8 T Cells ◽  
Chemokine Receptors ◽  
Cxcr3 Expression ◽  
Selective Suppression ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

We studied the expression of chemokine receptors CCR1, CCR2, CCR3, CCR5, and CXCR3 on CD4 and CD8 positive T cells, and on CD14 positive monocytes in blood from 10 patients with relapsing-remitting multiple sclerosis (MS) at initiation of interferon (IFN)- βtreatment, after 1 month and after 3 months of treatment. It was found that the expression of CXCR3 on CD4+ and CD8+ T cells was significantly reduced after 3 months of treatment. The expression of other receptors was unaltered. Since CXCR3 cells are enriched in cerebrospinal fluid (CSF), and are detected in lesion material in MS this may represent an important mode of action of interferon- βin MS.

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