Glatiramer acetate attenuates the pro-migratory profile of adhesion molecules on various immune cell subsets in multiple sclerosis

Sellner, Johann; Koczi, W.; Harrer, Andrea; Oppermann, Katrin; Obregon-Castrillo, E.; Pilz, Georg; Wipfler, Peter; Afazel, Shahrzad; Haschke-Becher, Elisabeth; Trinka, Eugen; Kraus, Jörg

doi:10.1111/cei.12125

Cited by 26 publications

(20 citation statements)

References 47 publications

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“…Expression of adhesion molecules on peripheral immune cells has been reported to be 1.5–3 fold higher in patients with MS and is associated with enhanced pro‐migratory capabilities . Whilst there were no significant differences in NK cell adhesion molecules in this cohort of patients with MS, mononuclear cells infiltrating MS brain lesions have been found to have upregulated expression of adhesion molecules .…”

Section: Discussionmentioning

confidence: 59%

“…Whilst there were no significant differences in NK cell adhesion molecules in this cohort of patients with MS, mononuclear cells infiltrating MS brain lesions have been found to have upregulated expression of adhesion molecules . Under inflammatory conditions, adhesion molecules have an enhanced affinity for their ligands on normal endothelial cells which can facilitate the extravasation of NK cells to inflammatory sites and into the CNS to mediate their effector functions . The adhesion molecule CD11b has been associated with disease severity of MS with a deficiency of CD11b linked to a delayed disease onset and the development of mild EAE symptoms .…”

Section: Discussionmentioning

confidence: 72%

“…It has been suggested that genetic disruption of CD94/NKG2A removes NK cell inhibition, enhancing cytotoxic lysis of pathogenic autoreactive CD4 + T cells and microglia in the central nervous system, favouring the remission state of MS and reducing the disease severity [21]. Expression of adhesion molecules on peripheral immune cells has been reported to be 1.5-3 fold higher in patients with MS and is associated with enhanced promigratory capabilities [34]. Whilst there were no significant differences in NK cell adhesion molecules in this cohort of patients with MS, mononuclear cells infiltrating MS brain lesions have been found to have upregulated expression of adhesion molecules [34,35].…”

Section: Discussionmentioning

confidence: 99%

“…Expression of adhesion molecules on peripheral immune cells has been reported to be 1.5-3 fold higher in patients with MS and is associated with enhanced promigratory capabilities [34]. Whilst there were no significant differences in NK cell adhesion molecules in this cohort of patients with MS, mononuclear cells infiltrating MS brain lesions have been found to have upregulated expression of adhesion molecules [34,35]. Under inflammatory conditions, adhesion molecules have an enhanced affinity for their ligands on normal endothelial cells which can facilitate the extravasation of NK cells to inflammatory sites and into the CNS to mediate their effector functions [34,35].…”

Section: Discussionmentioning

confidence: 99%

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Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis

et al. 2015

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Patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and multiple sclerosis (MS) suffer from debilitating fatigue which is not alleviated by rest. In addition to the fatigue-related symptoms suffered by patients with CFS/ME and MS, dysfunction of the immune system and, in particular, reduced natural killer (NK) cell cytotoxic activity has also been reported in CFS/ME and MS. The purpose of this pilot study was to compare NK cellular mechanisms in patients with CFS/ME and MS to investigate potential dysfunctions in the NK cell activity pathway. Flow cytometry protocols assessed CD56 dim CD16 + and CD56 bright CD16 +/À NK cell expression of adhesion molecules, NK activating and inhibiting receptors, NK cell maturation and lytic proteins. All participants in this study were female and included 14 patients with CFS/ME, nine patients with MS and 19 non-fatigued controls. The patient groups and the non-fatigued controls were not taking any immunosuppressive or immune-enhancing medications. In the MS cohort, KIR2DL5 was significantly increased on CD56 bright CD16 +/À NK cells and expression of CD94 was significantly increased on CD56 dim CD16 + NK cells in comparison with the controls. Co-expression of CD57 and perforin was significantly increased on CD56 dim CD16 + NK cells from patients with CFS/ME compared to the MS and non-fatigued control participants. The results from this pilot study suggest that NK cells from patients with CFS/ME and MS may have undergone increased differentiation in response to external stimuli which may affect different mechanisms in the NK cell cytotoxic activity pathway.

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis

et al. 2015

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“…Relapses are clearly defined attacks of deteriorating neurologic function and are followed by periods of partial or complete recovery. Relapses in MS patients are associated with heightened inflammatory immune response in the CNS and periphery including elevated levels of pro-inflammatory cytokines TNF-α IFN–γ and IL-6 [50] and decreased levels of the anti-inflammatory cytokine IL-10 [51], increased expression of CCR5 and CXCR3 [52] on circulating T cells, deficient CD4+CD25+ Treg function [53], upregulation of adhesion molecules on T-cells, B-cells and NK cells [54], higher levels of MMP-2 and MMP-14 in monocytes, and a significantly increased fraction of CD20+ B cells. Although the role of CD4+CD25+FoxP3+ Tregs in maintaining immune quiescence in MS has been known for a while now, scientists have, only recently, started appreciating the regulatory role of CD8+ T cells in MS. We identified an unexpected and novel association of the immune regulatory function of neuroantigen-specific CD8+ T cells with MS clinical state.…”

Section: The Indispensable Role Of Regulatory Cd8 T Cells In Maintainmentioning

confidence: 99%

Immune regulation of multiple sclerosis by CD8+ T cells

2014

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The role of CD8+ T cells in the process of autoimmune pathology has been both understudied and controversial. Multiple sclerosis (MS) is an inflammatory, demyelinating disorder of the central nervous system (CNS) with an underlying T-cell-mediated immunopathology. CD8+ T cells are the predominant T cells in human MS lesions, showing oligoclonal expansion at the site of pathology. It is still unclear whether these cells represent pathogenic immune responses or disease-regulating elements. Through studies in human MS and its animal model, experimental autoimmune encephalomyelitis (EAE), we have discovered two novel CD8+ T cell populations that play an essential immunoregulatory role in disease: (1) MHC class Ia-restricted neuroantigen-specific “autoregulatory” CD8+ T cells and (2) glatiramer acetate (GA/Copaxone®) therapy-induced Qa-1/HLA-E-restricted GA-specific CD8+ T cells. These CD8 Tregs suppress proliferation of pathogenic CD4+CD25- T-cells when stimulated by their cognate antigens. Similarly, CD8+ Tregs significantly suppress EAE when transferred either pre-disease induction or during peak disease. The mechanism of disease inhibition depends, at least in part, on an antigen-specific, contact-dependent process and works through modulation of CD4+ T cell responses as well as antigen presenting cells (APC) through a combination of cytotoxicity and cytokine-mediated modulation. This review provides an overview of our understanding of CD8+ T cells in immune-mediated disease, focusing particularly on our findings about regulatory CD8+ T cells both in MS and EAE. Clinical relevance of these novel CD8-regulatory populations is discussed, providing insights into a potentially intriguing, novel therapeutic strategy for these diseases.

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The role of NK and NKT cells in the pathogenesis and improvement of multiple sclerosis following disease‐modifying therapies

Ahmadi

Vastani

Abounoori

et al. 2022

Health Science Reports

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Background Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) that T cells become autoreactive by recognizing CNS antigens. Both innate and adaptive immune systems are involved in the pathogenesis of MS. In recent years, the impact of innate immune cells on MS pathogenesis has received more attention. CD56bright NK cells, as an immunoregulatory subset of NK cells, can increase the production of cytokines that modulate adaptive immune responses, whereas CD56dim NK cells are more active in cytolysis functions. These two main subsets of NK cells may have different effects on the onset or progression of MS. Invariant NKT (iNKT) cells are other immune cells involved in the control of autoimmune diseases; however, variant NKT (vNKT) cells, despite limited information, could play a role in MS remission via an immunoregulatory pathway. Aim We aimed to evaluate the influence of MS therapeutic agents on NK and NKT cells and NK cell subtypes. Materials and Methods The possible mechanism of each MS therapeutic agent has been presented here, focusing on the effects of different disease‐modifying therapies on the number of NK and NKT subtypes. Results Expansion of CD56bright NK cells, reduction in the CD56dim cells, and enhancement in NKT cells are the more important innate immune cells alterations following the disease‐modifying therapies. Conclusion Expansion of CD56bright NK cells or reduction in the CD56dim cells has been associated with a successful response to different treatments in MS. iNKT and vNKT cells could have beneficial effects on MS improving. It seems that they are enhanced due to some of MS drugs, leading to disease improvement. However, a reduction in the number of NKT cells could be due to the adverse effects of some of MS drugs on the bone marrow.

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Glatiramer acetate attenuates the pro-migratory profile of adhesion molecules on various immune cell subsets in multiple sclerosis

Cited by 26 publications

References 47 publications

Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis

Pilot Study of Natural Killer Cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Multiple Sclerosis

Immune regulation of multiple sclerosis by CD8+ T cells

The role of NK and NKT cells in the pathogenesis and improvement of multiple sclerosis following disease‐modifying therapies

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