Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/90920
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dc.contributor.authorNa, S.Y.en
dc.contributor.authorCao, Y.en
dc.contributor.authorToben, C.en
dc.contributor.authorNitschke, L.en
dc.contributor.authorStadelmann, C.en
dc.contributor.authorGold, R.en
dc.contributor.authorSchimpl, A.en
dc.contributor.authorHunig, T.en
dc.date.issued2008en
dc.identifier.citationBrain, 2008; 131(9):2353-2365en
dc.identifier.issn0006-8950en
dc.identifier.issn1460-2156en
dc.identifier.urihttp://hdl.handle.net/2440/90920-
dc.description.abstractIn multiple sclerosis, CD8 T-cells are thought play a key pathogenetic role, but mechanistic evidence from rodent models is limited. Here, we have tested the encephalitogenic potential of CD8 T-cells specific for the model antigen ovalbumin (OVA) sequestered in oligodendrocytes as a cytosolic molecule. We show that in these ‘ODC-OVA’ mice, the neo-self antigen remains invisible to CD4 cells expressing the OVA-specific OT-II receptor. In contrast, OVA is accessible to naïve CD8 T-cells expressing the OT-I T-cell receptor, during the first 10 days of life, resulting in antigen release into the periphery. Introduction of OT-I as a second transgene leads to fulminant demyelinating experimental autoimmune encephalomyelitis with multiple sclerosis-like lesions, affecting cerebellum, brainstem, optic nerve and spinal cord. OVA-transgenic oligodendrocytes activate naïve OT-I cells in vitro, and both major histocompatibility complex class I expression and the OT-I response are further up-regulated by interferon-γ (IFN-γ). Release of IFN-γ into the circulation of ODC-OVA/OT-I double transgenic mice precedes disease manifestation, and pathogenicity of OT-I cells transferred into ODC-OVA mice is largely IFN-γ dependent. In conclusion, naïve CD8 T-cells gaining access to an ‘immune-privileged’ organ can initiate autoimmunity via an IFN-γ-assisted amplification loop even if the self-antigen in question is not spontaneously released for presentation by professional antigen presenting cells.en
dc.description.statementofresponsibilityShin-Young Na, Yi Cao, Catherine Toben, Lars Nitschke, Christine Stadelmann, Ralf Gold, Anneliese Schimpl, and Thomas Hünigen
dc.language.isoenen
dc.publisherOxford University Pressen
dc.rights© The Author (2008).en
dc.subjectautoimmune encephalitis; multiple sclerosis; cytotoxic T-cell response; demyelinating disease; blood-brain barrieren
dc.titleNaive CD8 T-cells initiate spontaneous autoimmunity to a sequestered model antigen of the central nervous systemen
dc.typeJournal articleen
dc.identifier.doi10.1093/brain/awn148en
pubs.publication-statusPublisheden
dc.identifier.orcidToben, C. [0000-0001-8399-4108]en
Appears in Collections:Medicine publications

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