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https://hdl.handle.net/2440/90920
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dc.contributor.author | Na, S.Y. | - |
dc.contributor.author | Cao, Y. | - |
dc.contributor.author | Toben, C. | - |
dc.contributor.author | Nitschke, L. | - |
dc.contributor.author | Stadelmann, C. | - |
dc.contributor.author | Gold, R. | - |
dc.contributor.author | Schimpl, A. | - |
dc.contributor.author | Hunig, T. | - |
dc.date.issued | 2008 | - |
dc.identifier.citation | Brain: a journal of neurology, 2008; 131(9):2353-2365 | - |
dc.identifier.issn | 0006-8950 | - |
dc.identifier.issn | 1460-2156 | - |
dc.identifier.uri | http://hdl.handle.net/2440/90920 | - |
dc.description.abstract | In 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. | - |
dc.description.statementofresponsibility | Shin-Young Na, Yi Cao, Catherine Toben, Lars Nitschke, Christine Stadelmann, Ralf Gold, Anneliese Schimpl, and Thomas Hünig | - |
dc.language.iso | en | - |
dc.publisher | Oxford University Press | - |
dc.rights | © The Author (2008). | - |
dc.source.uri | http://dx.doi.org/10.1093/brain/awn148 | - |
dc.subject | autoimmune encephalitis; multiple sclerosis; cytotoxic T-cell response; demyelinating disease; blood-brain barrier | - |
dc.title | Naive CD8 T-cells initiate spontaneous autoimmunity to a sequestered model antigen of the central nervous system | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1093/brain/awn148 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Toben, C. [0000-0001-8399-4108] | - |
Appears in Collections: | Aurora harvest 7 Medicine publications |
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