Cell-Based Modulation of Autoimmune Responses in Multiple Sclerosis and Experimental Autoimmmune Encephalomyelitis: Therapeutic Implications

Mastorodemos, Vasileios; Ιωάννου, Μαριάννα; Verginis, Panayotis

doi:10.1159/000362370

Cited by 35 publications

(32 citation statements)

References 161 publications

(176 reference statements)

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“…Other T cell subsets analyzed did not demonstrate any changes in cytokine production at the population level. Initially, IFN-γ was considered the key pathogenic cytokine in MS, but its role in the disease has been questioned during recent years (1, 35, 36). However, a number of findings support a disease-promoting role for this cytokine.…”

Section: Discussionmentioning

confidence: 99%

High Interferon-γ Uniquely in Vδ1 T Cells Correlates with Markers of Inflammation and Axonal Damage in Early Multiple Sclerosis

et al. 2017

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We have identified a population of T lymphocytes in peripheral blood, Vδ1 TCRγδ T lymphocytes, which unexpectedly was uniquely expressing high production of interferon-γ in newly diagnosed, untreated multiple sclerosis (MS) patients. IFN-γ production in this population distinctly correlated to parameters of clinical disease activity, inflammation, and neuronal damage. These Vδ1 T lymphocytes belong to a population of innate T lymphocytes that recognize antigen in the context of CD1d/CD1c and which include reactivity to the myelin glycosphingolipid sulfatide. Importantly, patients treated with natalizumab, blocking leukocyte transmigration to central nervous system, had completely normalized levels of interferon-γ-producing Vδ1 T lymphocytes. A biomarker and early sign of demyelinating disease in MS is much warranted and would help identify immunopathogenesis and prognosis of disease as well as monitor success with adequate treatment. The present study identifies the Vδ1 T lymphocytes as an early marker of MS and a possible link to understanding the disease etiology.

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Section: Discussionmentioning

confidence: 99%

High Interferon-γ Uniquely in Vδ1 T Cells Correlates with Markers of Inflammation and Axonal Damage in Early Multiple Sclerosis

et al. 2017

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“…The clinical onset of MS in patients usually manifests in their 20s and 30s and affects women about twice as often as men. While the etiologies in MS are hotly debated, the evidence obtained from animal models and patient studies indicated that abnormalities in the activity of different types of lymphocytes and the accompanying dysregulation of inflammatory cytokines play a crucial role in the pathogenesis of MS (Mastorodemos et al, 2015). So far, there has been SIGNIFICANCE Current therapeutic approaches can only ameliorate the clinical symptoms or reduce the frequency of relapse in multiple sclerosis.…”

Section: Introductionmentioning

confidence: 99%

Diversity of immune cell types in multiple sclerosis and its animal model: Pathological and therapeutic implications

Cheng

Sun

Xie

et al. 2017

J of Neuroscience Research

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Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system with an autoimmune attack on the components of the myelin sheath and axons. The etiology of the disease remains largely unknown, but it is commonly acknowledged that the development of MS probably results from the interaction of environmental factors in conjunction with a genetic predisposition. Current therapeutic approaches can only ameliorate the clinical symptoms or reduce the frequency of relapse in MS. Most drugs used in this disease broadly suppress the functions of immune effector cells, which can result in serious side effects. Thus, new therapeutic methods resulting in greater efficacy and lower toxicity are needed. Toward this end, cellbased therapies are of increasing interest in the treatment of MS. Several immunoregulatory cell types, including regulatory Tcells, regulatory B cells, M2 macrophages, tolerogenic dendritic cells, and stem cells, have been developed as novel therapeutic tools for the treatment of MS. In this Review, we summarize studies on the application of these cell populations for the treatment of MS and its animal model, experimental autoimmune encephalomyelitis, and call for further research on applications and mechanisms by which these cells act in the treatment of MS.

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“…Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS) [19]. EAE is also an inflammatory disease induced by CD4 + T cells [20].…”

Section: Introductionmentioning

confidence: 99%

Apoptotic cell-treated dendritic cells induce immune tolerance by specifically inhibiting development of CD4+ effector memory T cells

2015

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CD4+ memory T cells play an important role in induction of autoimmunity and chronic inflammatory responses; however, regulatory mechanisms of CD4+ memory T cell-mediated inflammatory responses are poorly understood. Here we show that apoptotic cell-treated dendritic cells inhibit development and differentiation of CD4+ effector memory T cells in vitro and in vivo. Simultaneously, i.v. transfer of apoptotic T cell-induced tolerogenic dendritic cells can block development of experimental autoimmune encephalomyelitis (EAE), an inflammatory disease of the central nervous system in C57 BL/6J mouse. Our results imply that it is effector memory CD4+ T cells, not central memory CD4+ T cells, which play a major role in chronic inflammatory responses in mice with EAE. I.V. transfer of tolerogenic dendritic cells induced by apoptotic T cells leads to immune tolerance by specifically blocking development of CD4+ effector memory T cells compared with results of EAE control mice. These results reveal a new mechanism of apoptotic cell-treated dendritic cell-mediated immune tolerance in vivo

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Cell-Based Modulation of Autoimmune Responses in Multiple Sclerosis and Experimental Autoimmmune Encephalomyelitis: Therapeutic Implications

Cited by 35 publications

References 161 publications

High Interferon-γ Uniquely in Vδ1 T Cells Correlates with Markers of Inflammation and Axonal Damage in Early Multiple Sclerosis

High Interferon-γ Uniquely in Vδ1 T Cells Correlates with Markers of Inflammation and Axonal Damage in Early Multiple Sclerosis

Diversity of immune cell types in multiple sclerosis and its animal model: Pathological and therapeutic implications

Apoptotic cell-treated dendritic cells induce immune tolerance by specifically inhibiting development of CD4+ effector memory T cells

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