T-cell Responses to Myelin Antigens in Multiple Sclerosis; Relevance of the Predominant Autoimmune Reactivity to Myelin Oligodendrocyte Glycoprotein

1998 ◽  
Vol 11 (4) ◽  
pp. 287-299 ◽  
Author(s):  
Nicole Kerlero de Rosbo ◽  
Avraham Ben-Nun
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
T Cell Responses ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Cell Responses ◽  
Myelin Antigens ◽  
Autoimmune Reactivity

Myelin reactive T cells in the autoimmune pathogenesis of multiple sclerosis

1998 ◽  
Vol 4 (3) ◽  
pp. 203-211 ◽  
Author(s):  
Piet Stinissen ◽  
Robert Medaer ◽  
Jef Raus
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Chronic Inflammatory Disease ◽  
Current Evidence ◽  
Central Position ◽  
Cell Responses ◽  
The Central Nervous System ◽  
Myelin Antigens

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) leading to demyelination. Although it is widely accepted that demyelination in MS results from an active inflammatory process, the cause of the inflammation is still not completely resolved. Findings in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and observations in human MS have led to the hypothesis that MS is an autoimmune disease mediated by autoreactive T cells with specificity for myelin antigens. The identity of the brain antigen(s) which is (are) the primary target(s) of the autoimmune process is not known, but current evidence indicates that myelin basic protein (MBP) is a likely candidate. In this paper we will overview some of the experimental evidence suggesting that MBP reactive T cells hold a central position in the pathogenesis of MS, and discuss some of the currently tested therapeutic strategies in MS which are directed towards the pathogenic MBP reactive T cells. Although there appears to be no direct correlation between anti-MBP T cell responses and clinical disease activity, some recent observations suggest that monitoring of anti-MBP T cell responses could be helpful to study immunological efficacy of experimental immunotherapies in MS.

scholarly journals Multiple sclerosis: B- and T-cell responses to the extracellular domain of the myelin oligodendrocyte glycoprotein

Brain ◽  
1999 ◽  
Vol 122 (11) ◽  
pp. 2089-2100 ◽  
Author(s):  
Ralf-Björn Lindert ◽  
Claus G. Haase ◽  
Uschi Brehm ◽  
Christopher Linington ◽  
Hartmut Wekerle ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
T Cell Responses ◽  
Extracellular Domain ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Cell Responses

scholarly journals Effect of Myelin Oligodendrocyte Glycoprotein (MOG35-55) on Cell Differentiation and Abzymes Production in Transgenic EAE-Prone Th Mice with T Cells Response During the Development of Experimental Encephalomyelitis

2021 ◽  
Author(s):  
Kseniya Aulova ◽  
Andrey Urusov ◽  
Ludmila Toporkova ◽  
Sergey Sedykh ◽  
Yuliya Shevchenko ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Bone Marrow ◽  
T Cell ◽  
T Cell Responses ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Autoimmune Reaction ◽  
Hematopoietic Stem ◽  
Male And Female ◽  
Female Mice ◽  
Cell Responses

Abstract Background: The mechanisms of multiple sclerosis development are still unknown. It was shown that the development of experimental autoimmune encephalomyelitis (EAE) in EAE prone C57BL/6 mice (model mimicking human multiple sclerosis) having B and T lymphocyte responses is associated with modification in the differentiation profiles of bone marrow hematopoietic stem cells (HSCs) and the increase in lymphocyte proliferation. Methods: Only T cell responses characterize other EAE transgenic prone Th mice. Different characteristics of the autoimmune reaction in Th mice were analyzed. During the development of EAE (and inflammation processes), the differentiation profiles of Th mice bone marrow HSCs (BFU-E, CFU-E, CFU-GM, CFU-GEMM, T, and B lymphocytes) were noticeably or significantly different in male and female mice before and after their immunization with myelin oligodendrocyte glycoprotein (MOG35-55). Results: The patterns of B and T (including CD4 and CD8 cells) lymphocytes proliferation in several organs (spleen, thymus, bone marrow, blood, and lymph nodes) during spontaneous (completely untreated mice) and MOG-treatment-accelerated development of EAE was also remarkably or significantly different in male and female mice. All these changes in male and female mice, despite some differences, were coupled with the increase in the concentrations of autoantibodies against DNA, myelin basic protein, and MOG, and with the increase in the relative activity of catalytic antibodies hydrolyzing these antigens. Conclusions: A comparison of the changes in a large number of parameters characterizing the development of EAE in Th and C57BL/6 mice was carried out. It was shown that MOG very much accelerates the development of EAE in Th mice with T cell responses. Despite some differences, the general patterns of the developing of spontaneous and MOG-accelerated EAE in Th male and female mice and in C57BL/6 mice are similar to a notable extent.

scholarly journals T-cell responses to myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis

1998 ◽  
Vol 90 (1) ◽  
pp. 33
Author(s):  
C. Ewing ◽  
M. Honeyman ◽  
L.C. Harrison ◽  
J. Bettadapura ◽  
K. Menon ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
T Cell Responses ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Cell Responses

scholarly journals Aberrant T cell responses to myelin antigens during clinical exacerbation in patients with multiple sclerosis

2000 ◽  
Vol 12 (12) ◽  
pp. 1641-1650 ◽  
Author(s):  
Maria V. Tejada-Simon ◽  
Ying C. Q. Zang ◽  
Deye Yang ◽  
Jian Hong ◽  
Sufang Li ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
T Cell Responses ◽  
Cell Responses ◽  
Myelin Antigens

Thymic involution and proliferative T-cell responses in multiple sclerosis

2010 ◽  
Vol 221 (1-2) ◽  
pp. 73-80 ◽  
Author(s):  
Danielle A. Duszczyszyn ◽  
Julia L. Williams ◽  
Helen Mason ◽  
Yves Lapierre ◽  
Jack Antel ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
T Cell Responses ◽  
Thymic Involution ◽  
Cell Responses

T cell response to two immunodominant proteolipid protein (PLP) peptides in multiple sclerosis patients and healthy controls

1996 ◽  
Vol 1 (5) ◽  
pp. 270-278 ◽  
Author(s):  
CM Pelfrey ◽  
LR Tranquill ◽  
AB Vogt ◽  
HF McFarland
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Demyelinating Disease ◽  
T Cell Responses ◽  
Proteolipid Protein ◽  
T Cell Response ◽  
Healthy Controls ◽  
Cell Responses ◽  
Hla Binding ◽  
Multiple Sclerosis Patients

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system in which autoimmune T lymphocytes reacting with myelin antigens are believed to play a pathogenic role. Since HLA binding is involved in the selection of T cell responses, we have examined PLP peptide binding to HLA DR2, an HLA allele frequently found in MS patients. Both PLP 40–60 and PLP 89–106 show significant, high affinity binding to HLA DR2. We then tested whether responses to PLP peptides 40–60 and 89–106 are elevated in multiple sclerosis patients compared to matched controls. We also analysed T cell responses to MBP 87–106, which is considered to be the immunodominant region of MBP in humans. Here we demonstrate heterogenous T cell responses to PLP 40–60, PLP 89–106 and MBP 87–106 in both MS patients and controls. The overall number of TCL and the HLA restriction of those TCL did not vary significantly in the two groups. PLP 40–60 specific cytolytic TCL were increased in MS patients, whereas healthy controls had increased percentages of cytolytic TCL responding to PLP 89–106 and MBP 87–106. Although the data presented here shows heterogenous responses in T cell numbers, differences in numbers and specificity of cytolytic cells could be involved in the pathogenesis of autoimmune demyelinating disease.

scholarly journals Ectopic Lymphoid Follicles in Multiple Sclerosis: Centers for Disease Control?

2020 ◽  
Vol 11 ◽  
Author(s):  
Austin Negron ◽  
Olaf Stüve ◽  
Thomas G. Forsthuber
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
T Cell Responses ◽  
Memory B Cells ◽  
Lymphoid Follicles ◽  
Cell Responses ◽  
B Cell Responses

While the contribution of autoreactive CD4+ T cells to the pathogenesis of Multiple Sclerosis (MS) is widely accepted, the advent of B cell-depleting monoclonal antibody (mAb) therapies has shed new light on the complex cellular mechanisms underlying MS pathogenesis. Evidence supports the involvement of B cells in both antibody-dependent and -independent capacities. T cell-dependent B cell responses originate and take shape in germinal centers (GCs), specialized microenvironments that regulate B cell activation and subsequent differentiation into antibody-secreting cells (ASCs) or memory B cells, a process for which CD4+ T cells, namely follicular T helper (TFH) cells, are indispensable. ASCs carry out their effector function primarily via secreted Ig but also through the secretion of both pro- and anti-inflammatory cytokines. Memory B cells, in addition to being capable of rapidly differentiating into ASCs, can function as potent antigen-presenting cells (APCs) to cognate memory CD4+ T cells. Aberrant B cell responses are prevented, at least in part, by follicular regulatory T (TFR) cells, which are key suppressors of GC-derived autoreactive B cell responses through the expression of inhibitory receptors and cytokines, such as CTLA4 and IL-10, respectively. Therefore, GCs represent a critical site of peripheral B cell tolerance, and their dysregulation has been implicated in the pathogenesis of several autoimmune diseases. In MS patients, the presence of GC-like leptomeningeal ectopic lymphoid follicles (eLFs) has prompted their investigation as potential sources of pathogenic B and T cell responses. This hypothesis is supported by elevated levels of CXCL13 and circulating TFH cells in the cerebrospinal fluid (CSF) of MS patients, both of which are required to initiate and maintain GC reactions. Additionally, eLFs in post-mortem MS patient samples are notably devoid of TFR cells. The ability of GCs to generate and perpetuate, but also regulate autoreactive B and T cell responses driving MS pathology makes them an attractive target for therapeutic intervention. In this review, we will summarize the evidence from both humans and animal models supporting B cells as drivers of MS, the role of GC-like eLFs in the pathogenesis of MS, and mechanisms controlling GC-derived autoreactive B cell responses in MS.

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