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- Title
Primary oligodendrocyte death does not elicit anti-CNS immunity.
- Authors
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
- Abstract
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.
- Subjects
MYELIN; CENTRAL nervous system -- Immunology; MULTIPLE sclerosis; MYELIN oligodendrocyte glycoprotein; LABORATORY mice; ANTIGENS; LYMPHOCYTES; T cells
- Publication
Nature Neuroscience, 2012, Vol 15, Issue 4, p543
- ISSN
1097-6256
- Publication type
Article
- DOI
10.1038/nn.3062