T-cell reactivity to multiple myelin antigens in multiple sclerosis patients and healthy controls

Hellings, Niels; Baree, Mark; Verhoeven, Christof; D'hooghe, Marie B; Medaer, Robert; Bernard, Carole; Raus, Jef; Stinissen, Piet

doi:10.1002/1097-4547(20010201)63:3<290::aid-jnr1023>3.0.co;2-4

Cited by 125 publications

(83 citation statements)

References 41 publications

(41 reference statements)

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“…In particular, we did not find differences in proliferative responses of myelin-specific and presumably autoreactive T eff cells obtained from MS patients and healthy control individuals. The degree of antigen-specific T eff proliferation was in concordance with proliferative T cell responses towards rhMOG observed in other studies [31][32][33][34]. rhMOG preparations used in this study were tested to be free of endotoxin by HPLC, and in vitro stimulation with b2-microglobulin obtained from the same E. coli expression system did not induce detectable T cell proliferation as previously demonstrated [27].…”

Section: T Reg Derived From Ms Patients Exhibit Reduced Suppressive Psupporting

confidence: 89%

Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis

et al. 2005

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Immunoregulatory T cells of CD4 + CD25 + phenotype suppress T cell function and protect rodents from organ-specific autoimmune disease. The human counterpart of this subset of T cells expresses high levels of CD25 and its role in human autoimmune disorders is currently under intense investigation. In multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS), the activation of circulating self-reactive T cells with specificity for myelin components is considered to be an important disease initiating event. Here, we investigated whether MS is associated with an altered ability of CD4 + CD25 high regulatory T cells (T reg ) to confer suppression of myelin-specific immune responses. Whereas T reg frequencies were equally distributed in blood and cerebrospinal fluid of MS patients and did not differ compared to healthy controls, the suppressive potency of patient-derived CD4 + CD25 high T lymphocytes was impaired. Their inhibitory effect on antigen-specific T cell proliferation induced by human recombinant myelin oligodendrocyte protein as well as on immune responses elicited by polyclonal and allogeneic stimuli was significantly reduced compared to healthy individuals. The effect was persistent and not due to responder cell resistance or altered survival of T reg , suggesting that a defective immunoregulation of peripheral T cells mediated by CD4 + CD25 high T lymphocytes promotes CNS autoimmunity in MS.

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Section: T Reg Derived From Ms Patients Exhibit Reduced Suppressive Psupporting

confidence: 89%

Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis

et al. 2005

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“…T H 2 cells produce the anti-inflammatory cytokines IL-4, IL-5, IL-10, IL-13, and transforming growth factor β. Studies have demonstrated the presence and activation of myelinreactive T cells in the blood and cerebrospinal fluid (CSF) of MS patients [8][9]. The T H 1 cells of MS patients are biased toward myelin basic protein (MBP) and proteolipid protein reactive cells [10].…”

Section: Multiple Sclerosis: An Inflammatory Diseasementioning

confidence: 89%

Oligodendrocyte cell death in pathogenesis of multiple sclerosis: Protection of oligodendrocytes from apoptosis by complement

Cudrici

Niculescu²,

Niculescu³

et al. 2006

JRRD

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Abstract-Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. It is mediated by activated lymphocytes, macrophages, microglia, and complement. In MS, myelin-forming oligodendrocytes (OLGs) are the targets of inflammatory and immune attacks. OLG death by apoptosis or necrosis causes the cell loss seen in MS plaques. Studies of experimental allergic encephalomyelitis (EAE) in caspase 11-deficient mice show that caspasemediated death of OLGs is critical to demyelination. Complement activation may affect MS pathogenesis through activated terminal complex C5b-9, which promotes demyelination, and through sublytic C5b-9, which protects OLGs from apoptosis. By inducing EAE in C5-deficient mice, we showed that complement C5 promotes axon preservation and new myelin formation, which protect OLGs from apoptosis. These findings indicate that activated complement C5b-9 plays a proinflammatory role in acute MS but may also protect OLGs from death in chronic MS.

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“…Although useful, these bulk methods are deficient in that they fail to provide information about functional responses of individual lymphocyte subsets (Maino et al, 1995). While ELI-SPOT assays evaluate the relative number of myelin-specific T lymphocytes able to produce cytokine of either Th1 or Th2 type (Hellings et al, 2001;Pelfrey et al, 2000), they measure only one aspect of the reactivity of T cells to a particular antigen, the cytokine production. The strength of our assay is that it measures both antigen-specific proliferation and cytokine production while using a small number of PBMC.…”

Section: Discussionmentioning

confidence: 99%

“…As IFN-γ is still the most commonly measured Th1 cytokine (Hellings et al, 2001;Vergelli et al, 2001;Weissert et al, 2002) and has been shown to be involved in MS pathogenesis (Panitch et al, 1987;Woodroofe and Cuzner, 1993), we limited our results presented here to IFN-γ production by myelin-specific T cells. To avoid bias, analysis of the flow cytometrybased assay was performed without the evaluator knowing the patients' clinical status.…”

Section: Flow Cytometry-based Assaymentioning

confidence: 99%

A new approach for evaluating antigen-specific T cell responses to myelin antigens during the course of multiple sclerosis

Arbour

Holz

Sipe

et al. 2003

Journal of Neuroimmunology

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We used a flow cytometry assay to measure proliferation and cytokine production of self-antigenspecific T cells in individual patients during the clinical course of multiple sclerosis (MS). Myelinassociated oligodendrocytic basic protein (MOBP) was selected for proof of principles in the assay, along with myelin basic protein (MBP) to assess specific activated T cells in 10 MS patients over an 18-month period, in parallel with brain magnetic resonance imaging (MRI) scans and clinical rating scale. A positive correlation occurred between antigen-specific T cell proliferation and interferon-γ production with clinical relapses and MRI lesion activity that was absent when the same patients were in remission.

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T-cell reactivity to multiple myelin antigens in multiple sclerosis patients and healthy controls

Cited by 125 publications

References 41 publications

Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis

Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis

Oligodendrocyte cell death in pathogenesis of multiple sclerosis: Protection of oligodendrocytes from apoptosis by complement

A new approach for evaluating antigen-specific T cell responses to myelin antigens during the course of multiple sclerosis

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