Primary oligodendrocyte death does not elicit anti-CNS immunity.

Locatelli, Giuseppe; Wörtge, Simone; Buch, Thorsten; Ingold, Barbara; Frommer, Friederike; Sobottka, Bettina; Krüger, Martin; Karram, Khalad; Bühlmann, Claudia; Bechmann, Ingo; Heppner, Frank L; Waisman, Ari; Becher, Burkhard (2012). Primary oligodendrocyte death does not elicit anti-CNS immunity. Nature neuroscience, 15(4), pp. 543-550. Nature America 10.1038/nn.3062

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Anti-myelin immunity is commonly thought to drive multiple sclerosis, yet the initial trigger of this autoreactivity remains elusive. One of the proposed factors for initiating this disease is the primary death of oligodendrocytes. To specifically test such oligodendrocyte death as a trigger for anti-CNS immunity, we inducibly killed oligodendrocytes in an in vivo mouse model. Strong microglia-macrophage activation followed oligodendrocyte death, and myelin components in draining lymph nodes made CNS antigens available to lymphocytes. However, even conditions favoring autoimmunity-bystander activation, removal of regulatory T cells, presence of myelin-reactive T cells and application of demyelinating antibodies-did not result in the development of CNS inflammation after oligodendrocyte death. In addition, this lack of reactivity was not mediated by enhanced myelin-specific tolerance. Thus, in contrast with previously reported impairments of oligodendrocyte physiology, diffuse oligodendrocyte death alone or in conjunction with immune activation does not trigger anti-CNS immunity.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Locatelli, Giuseppe

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1097-6256

Publisher:

Nature America

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

22 Mar 2018 16:43

Last Modified:

05 Dec 2022 15:10

Publisher DOI:

10.1038/nn.3062

PubMed ID:

22366759

URI:

https://boris.unibe.ch/id/eprint/111250

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