Oligodendrocytes in the early course of multiple sclerosis

Brück, Wolfgang; Schmied, M.; Suchanek, Gerda; Brück, Yvonne; Breitschopf, Helene; Poser, S.; Piddlesden, Sara J.; Lassmann, Hans

doi:10.1002/ana.410350111

Cited by 197 publications

(104 citation statements)

References 27 publications

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“…minor myelin constituents like CNPase or MOG. Lesions or lesional areas containing macrophages positive for minor myelin proteins reflect recent demyelination and are therefore classified as early active lesions (7,8). Since ␣B-crystallin is a minor myelin constituent, one would expect the detectability of this protein inside macrophages to be limited.…”

Section: Discussionmentioning

confidence: 99%

“…To locally (re)activate T cells, a potential autoantigen must be presented to the cellular immune system. In immunologically active MS lesions, characterized by ongoing or recent demyelination and the presence of inflammatory infiltrates, several myelin proteins can be detected in macrophages (7), suggesting processing and presentation of these proteins to the cellular immune system.…”

Section: Ultiple Sclerosis (Ms)mentioning

confidence: 99%

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Presentation of αB-Crystallin to T Cells in Active Multiple Sclerosis Lesions: An Early Event Following Inflammatory Demyelination

Bajramović

Plomp

Goes

et al. 2000

The Journal of Immunology

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In the development of multiple sclerosis (MS), (re)activation of infiltrating T cells by myelin-derived Ags is considered to be a crucial step. Previously, αB-crystallin has been shown to be an important myelin Ag to human T cells. Since αB-crystallin is an intracellular heat shock protein, the question arises at what stage, if any, during lesional development in MS this Ag becomes available for CD4+ T cells. In 3 of 10 active MS lesions, αB-crystallin could be detected inside phagocytic vesicles of perivascular macrophages, colocalizing with myelin basic protein and myelin oligodendrocyte glycoprotein (MOG). Although the detectability of MOG in phagosomes is considered as a marker for very recent demyelination, MOG was detected in more macrophages and in more lesions than αB-crystallin. The disappearance of αB-crystallin from macrophages even before MOG was confirmed by in vitro studies; within 6 h after myelin-uptake αB-crystallin disappears from the phagosomes. αB-Crystallin-containing macrophages colocalized with infiltrating T cells and they were characterized by expression of MHC class II, CD40, and CD80. To examine functional presentation of myelin Ags to T cells, purified macrophages were pulsed in vitro with whole myelin membranes. These macrophages activated both myelin-primed and αB-crystallin-primed T cells in terms of proliferation and IFN-γ secretion. In addition, αB-crystallin-pulsed macrophages activated myelin-primed T cells to the same extent as myelin-pulsed macrophages, whereas myelin basic protein-pulsed macrophages triggered no response at all. These data indicate that, in active MS lesions, αB-crystallin is available for functional presentation to T cells early during inflammatory demyelination.

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Section: Discussionmentioning

confidence: 99%

Section: Ultiple Sclerosis (Ms)mentioning

confidence: 99%

Presentation of αB-Crystallin to T Cells in Active Multiple Sclerosis Lesions: An Early Event Following Inflammatory Demyelination

Bajramović

Plomp

Goes

et al. 2000

The Journal of Immunology

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“…and C.S. according to criteria described elsewhere (Brück et al, 1995, 1994; Kutzelnigg et al, 2005; Lassmann, 2011; Lucchinetti et al, 2000; Schuh et al, 2014). The study was performed in accordance with national and local ethics regulations and approved by the UMG ethics committee.…”

Section: Methodsmentioning

confidence: 99%

Acutely damaged axons are remyelinated in multiple sclerosis and experimental models of demyelination

Schultz

Meer

Wrzos

et al. 2017

Glia

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Remyelination is in the center of new therapies for the treatment of multiple sclerosis to resolve and improve disease symptoms and protect axons from further damage. Although remyelination is considered beneficial in the long term, it is not known, whether this is also the case early in lesion formation. Additionally, the precise timing of acute axonal damage and remyelination has not been assessed so far. To shed light onto the interrelation between axons and the myelin sheath during de‐ and remyelination, we employed cuprizone‐ and focal lysolecithin‐induced demyelination and performed time course experiments assessing the evolution of early and late stage remyelination and axonal damage. We observed damaged axons with signs of remyelination after cuprizone diet cessation and lysolecithin injection. Similar observations were made in early multiple sclerosis lesions. To assess the correlation of remyelination and axonal damage in multiple sclerosis lesions, we took advantage of a cohort of patients with early and late stage remyelinated lesions and assessed the number of APP‐ and SMI32‐ positive damaged axons and the density of SMI31‐positive and silver impregnated preserved axons. Early de‐ and remyelinating lesions did not differ with respect to axonal density and axonal damage, but we observed a lower axonal density in late stage demyelinated multiple sclerosis lesions than in remyelinated multiple sclerosis lesions. Our findings suggest that remyelination may not only be protective over a long period of time, but may play an important role in the immediate axonal recuperation after a demyelinating insult.

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“…Fluorescent signals were collected with a XM10 camera (Olympus, Tokyo, Japan) mounted on a BX51 epifluorescence microscope (Olympus) using a ×20 objective. All lesions were active demyelinating according to the criteria of Brück et al [17]. CD4…”

Section: Immunohistochemistrymentioning

confidence: 99%

Analysis of CD4+ CD8+ double-positive T cells in blood, cerebrospinal fluid and multiple sclerosis lesions

Waschbisch

Sammet

Schröder

et al. 2014

Clinical and Experimental Immunology

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Oligodendrocytes in the early course of multiple sclerosis

Cited by 197 publications

References 27 publications

Presentation of αB-Crystallin to T Cells in Active Multiple Sclerosis Lesions: An Early Event Following Inflammatory Demyelination

Presentation of αB-Crystallin to T Cells in Active Multiple Sclerosis Lesions: An Early Event Following Inflammatory Demyelination

Acutely damaged axons are remyelinated in multiple sclerosis and experimental models of demyelination

Analysis of CD4+ CD8+ double-positive T cells in blood, cerebrospinal fluid and multiple sclerosis lesions

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