scholarly journals Pathogenic T cell cytokines in multiple sclerosis

2019 ◽  
Vol 217 (1) ◽  
Author(s):  
Catriona A. Wagner ◽  
Pamela J. Roqué ◽  
Joan M. Goverman
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Young Adults ◽  
T Cell ◽  
Animal Models ◽  
Demyelinating Disease ◽  
The Central Nervous System ◽  
Autoimmune Etiology

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system that is believed to have an autoimmune etiology. As MS is the most common nontraumatic disease that causes disability in young adults, extensive research has been devoted to identifying therapeutic targets. In this review, we discuss the current understanding derived from studies of patients with MS and animal models of how specific cytokines produced by autoreactive CD4 T cells contribute to the pathogenesis of MS. Defining the roles of these cytokines will lead to a better understanding of the potential of cytokine-based therapies for patients with MS.

scholarly journals The Majority of Infiltrating CD8+ T Cells in the Central Nervous System of Susceptible SJL/J Mice Infected with Theiler's Virus Are Virus Specific and Fully Functional

2002 ◽  
Vol 76 (13) ◽  
pp. 6577-6585 ◽  
Author(s):  
Bong-Su Kang ◽  
Michael A. Lyman ◽  
Byung S. Kim
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
T Cell ◽  
Demyelinating Disease ◽  
Class I ◽  
Theiler's Virus ◽  
Ctl Response ◽  
The Central Nervous System ◽  
Ifn Γ

ABSTRACT Theiler's virus infection of the central nervous system (CNS) induces an immune-mediated demyelinating disease in susceptible mouse strains, such as SJL/J, and serves as a relevant infectious model for human multiple sclerosis. It has been previously suggested that susceptible SJL/J mice do not mount an efficient cytotoxic T-lymphocyte (CTL) response to the virus. In addition, genetic studies have shown that resistance to Theiler's virus-induced demyelinating disease is linked to the H-2D major histocompatibility complex class I locus, suggesting that a compromised CTL response may contribute to the susceptibility of SJL/J mice. Here we show that SJL/J mice do, in fact, generate a CD8+ T-cell response in the CNS that is directed against one dominant (VP3159-166) and two subdominant (VP111-20 and VP3173-181) capsid protein epitopes. These virus-specific CD8+ T cells produce gamma interferon (IFN-γ) and lyse target cells in the presence of the epitope peptides, indicating that these CNS-infiltrating CD8+ T cells are fully functional effector cells. Intracellular IFN-γ staining analysis indicates that greater than 50% of CNS-infiltrating CD8+ T cells are specific for these viral epitopes at 7 days postinfection. Therefore, the susceptibility of SJL/J mice is not due to the lack of an early functional Theiler's murine encephalomyelitis virus-specific CTL response. Interestingly, T-cell responses to all three epitopes are restricted by the H-2Ks molecule, and this skewed class I restriction may be associated with susceptibility to demyelinating disease.

Movement Disorders

2016 ◽  
pp. 619-624
Author(s):  
Anhar Hassan ◽  
Eduardo E. Benarroch
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Young Adults ◽  
Movement Disorders ◽  
Demyelinating Disease ◽  
Substantial Effect ◽  
The Central Nervous System

The most common inflammatory demyelinating disease of the central nervous system is multiple sclerosis, a disabling disorder that affects predominantly young adults between 20 and 50 years old. It affects women twice as often as men. Multiple sclerosis has a complex immunopathogenesis, variable prognosis, and an unpredictable course. Polygenic and environmental (possibly viral) factors probably have a substantial effect on susceptibility to multiple sclerosis.

scholarly journals Analysis of the Runx3 expression during experiemental autoimmune encephalomyelitis

2018 ◽  
Author(s):  
Beatriz Souza Lopes ◽  
Alessandro dos Santos Farias ◽  
Ana Maria Marques
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Demyelinating Disease ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Effector Activity ◽  
Runx3 Gene ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS), which is attributed to a self-sustaining autoimmune mechanism. The majority of the knowledge regarding MS autoagressive mechanisms is resultant of studies performed in its experimental model (mice) the experimental autoimmune encephalomyelitis (EAE).Although, the literature reports that the EAE is mediated by proinflammatory CD4+ T cells , isn’t completely clear how these cells (known as helper cells) would be able of initiate the disease when adoptively transferred to healthy animals.We believe that the Runx3 gene presents a central role in the progression and regulation of the effector activity in CD4+ encephalitogenic lymphocytes.

scholarly journals Activated mouse astrocytes and T cells express similar CD44 variants. Role of CD44 in astrocyte/T cell binding

1993 ◽  
Vol 122 (5) ◽  
pp. 1067-1077 ◽  
Author(s):  
H Haegel ◽  
C Tölg ◽  
M Hofmann ◽  
R Ceredig
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
T Cell ◽  
Primary Cultures ◽  
Cell Types ◽  
Mrna Levels ◽  
The Central Nervous System

The CD44 adhesion molecule is expressed by astrocytes, glial-type cells which exhibit features of accessory cells for immune responses in the central nervous system. In primary cultures of mouse astrocytes, we have observed that surface expression and mRNA levels of CD44 are induced following stimulation with either PMA, or tumor necrosis factor alpha plus gamma interferon. Comparison of CD44 splice variants expressed by astrocytes and a T cell hybridoma shows that upon activation, both cell types express a similar pattern of CD44 transcripts. Thus, in both cell types, CD44 transcripts are produced which contain additional exons, including the exon v6 (known to be expressed by in vivo activated lymphocytes and by metastatic variants of tumor cells) as well as variants of larger size. In the autoimmune disease multiple sclerosis, activated T cells cross the blood-brain barrier and lead to inflammation in the central nervous system. Analysis of mice with experimental allergic encephalomyelitis, frequently used as an animal model of multiple sclerosis, shows that CD44 is induced in vivo on glial cells surrounding inflammatory lesions. Using an in vitro model for adhesion between T cells and astrocytes, we have found a correlation between the activation state of these cells and their adhesion potential. Dose-dependent inhibition of adhesion by hyaluronate and by anti-CD44 monoclonal antibody KM81 shows that CD44 is involved in the adhesive interactions between T cells and astrocytes.

scholarly journals TGF-β in Mice Ameliorates Experimental Autoimmune Encephalomyelitis in Regulating NK Cell Activity

2019 ◽  
Vol 28 (9-10) ◽  
pp. 1155-1160 ◽  
Author(s):  
J. Xu ◽  
Y. Wang ◽  
H. Jiang ◽  
M. Sun ◽  
J. Gao ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Nk Cells ◽  
Nk Cell ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Experimental Autoimmune

Multiple sclerosis is a disease characterized by inflammation and demyelination located in the central nervous system. Experimental autoimmune encephalomyelitis (EAE) is the most common animal model for multiple sclerosis (MS). Although the roles of T cells in MS/EAE have been well investigated, little is known about the functions of other immune cells in the neuroinflammation model. Here we found that an essential cytokine transforming growth factor β (TGF-β) which could mediate the differentiation of Th17/regulatory T cells was implicated in the natural killer (NK) cells’ activity in EAE. In EAE mice, TGF-β expression was first increased at the onset and then decreased at the peak, but the expressions of TGF-β receptors and downstream molecules were not affected in EAE. When we immunized the mice with MOG antigen, it was revealed that TGF-β treatment reduced susceptibility to EAE with a lower clinical score than the control mice without TGF-β. Consistently, inflammatory cytokine production was reduced in the TGF-β treated group, especially with downregulated pathogenic interleukin-17 in the central nervous system tissue. Furthermore, TGF-β could increase the transcription level of NK cell marker NCR1 both in the spleen and in the CNS without changing other T cell markers. Meanwhile TGF-β promoted the proliferation of NK cell proliferation. Taken together, our data demonstrated that TGF-β could confer protection against EAE model in mice through NK cells, which would be useful for the clinical therapy of MS.

scholarly journals A Pathogenic Role for Myelin-Specific Cd8+ T Cells in a Model for Multiple Sclerosis

2001 ◽  
Vol 194 (5) ◽  
pp. 669-676 ◽  
Author(s):  
Eric S. Huseby ◽  
Denny Liggitt ◽  
Thea Brabb ◽  
Bryan Schnabel ◽  
Claes Öhlén ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Demyelinating Disease ◽  
Clinical Symptoms ◽  
Autoimmune Encephalomyelitis ◽  
Effector Cells ◽  
Cns Autoimmunity ◽  
The Central Nervous System

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) characterized by plaques of infiltrating CD4+ and CD8+ T cells. Studies of MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS, focus on the contribution of CD4+ myelin-specific T cells. The role of CD8+ myelin-specific T cells in mediating EAE or MS has not been described previously. Here, we demonstrate that myelin-specific CD8+ T cells induce severe CNS autoimmunity in mice. The pathology and clinical symptoms in CD8+ T cell–mediated CNS autoimmunity demonstrate similarities to MS not seen in myelin-specific CD4+ T cell–mediated EAE. These data suggest that myelin-specific CD8+ T cells could function as effector cells in the pathogenesis of MS.

scholarly journals Blood serum amino acids profile in patients with Multiple Sclerosis

2015 ◽  
Vol 26 (1) ◽  
pp. 50-53
Keyword(s):  
Multiple Sclerosis ◽  
Amino Acids ◽  
Central Nervous System ◽  
Nervous System ◽  
Blood Serum ◽  
Demyelinating Disease ◽  
Initial Step ◽  
Control Group ◽  
The Central Nervous System ◽  
Amino Acids Profile

Multiple sclerosis is the most common demyelinating disease of the central nervous system, affecting mostly young people. There were many risk factors for MS identified, however a direct cause of the disease is still unknown. Pathological changes in the SM lead to the myelin sheath damage around axons, what prevents proper transmission of nerve impulses in the central nervous system. The aim of this study was analyzing and comparing the amino acids profile in the blood serum of MS patients to control group of healthy individuals and evaluating the relationship between them. Significant (p<0.05) differences in the level of glutamate, aspartate and taurine in the blood serum of MS patients were revealed. A positive glutamate and aspartate level correlation in the serum has been demonstrated. Gender is significant only in the case of glutamate level in blood serum. The studies highlight the important role of neurotransmitters in MS and are the initial step in proteomic research.

Population screening for association of mitochondrial haplogroups BM, J, K and M with multiple sclerosis: interrelation between haplogroup J and MS in Persian patients

2005 ◽  
Vol 11 (6) ◽  
pp. 728-730 ◽  
Author(s):  
M Houshmand ◽  
M H Sanati ◽  
F Babrzadeh ◽  
A Ardalan ◽  
M Teimori ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Young Adults ◽  
Mitochondrial Dna ◽  
Mitochondrial Haplogroups ◽  
Mtdna Mutations ◽  
Pcr Rflp ◽  
The Central Nervous System ◽  
Normal Controls

Background: Multiple sclerosis (MS) is an immunological inflammatory disease of the central nervous system (CNS) which is chronically observed in young adults. On the basis of earlier studies, potential relatedness between MS and mitochondrial DNA (mtDNA) mutations was postulated. Materials and methods: 246 individuals were screened using the PCR-RFLP method, including 70 MS patients examined for mitochondrial haplogroups BM, J, K and M and 176, 149 and 70 normal controls examined for haplogroups BM and M, J and K, respectively. Results and discussion: Our analysis revealed a relatively high proportion of haplogroup BM in MS patients (∼26%) compared to normal controls (∼13%). In addition, a slightly significant increase of MS patients of haplogroup J (20% in MS patients versus 9.39% in normal controls at P-0.049), while haplogroups M and K did not show contribution to MS contingency (2.85 and 2.27%, respectively at P-1.000 in haplogroup M and 12.85 and 7.14% respectively at P-0.399 in haplogroup K).

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