title: Primary oligodendrocyte death does not elicit anti-CNS immunity.
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.
authors.affiliation: Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Locatelli
authors.forename: Simone
authors.initials: S
authors.lastname: Wörtge
authors.forename: Thorsten
authors.initials: T
authors.lastname: Buch
authors.forename: Barbara
authors.initials: B
authors.lastname: Ingold
authors.forename: Friederike
authors.initials: F
authors.lastname: Frommer
authors.forename: Bettina
authors.initials: B
authors.lastname: Sobottka
authors.forename: Martin
authors.initials: M
authors.lastname: Krüger
authors.forename: Khalad
authors.initials: K
authors.lastname: Karram
authors.forename: Claudia
authors.initials: C
authors.lastname: Bühlmann
authors.forename: Ingo
authors.initials: I
authors.lastname: Bechmann
authors.forename: Frank L
authors.initials: FL
authors.lastname: Heppner
authors.forename: Ari
authors.initials: A
authors.lastname: Waisman
authors.forename: Burkhard
authors.initials: B
authors.lastname: Becher
mesh_terms: D000818:Animals; D016923:Cell Death / Q000276:immunology; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology*; D055879:Gene Knock-In Techniques; D051379:Mice; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology; D009836:Oligodendroglia / Q000276:immunology* / Q000473:pathology*