Naive CD8 T-Cells Initiate Spontaneous Autoimmunity to a Sequestered Model Antigen of the Central Nervous System

Autor/inn/en	Na, Shin-Young; Cao, Yi; Toben, Catherine; Nitschke, Lars; Stadelmann, Christine; Gold, Ralf; Schimpl, Anneliese; Hunig, Thomas
Titel	Naive CD8 T-Cells Initiate Spontaneous Autoimmunity to a Sequestered Model Antigen of the Central Nervous System
Quelle	In: Brain, 131 (2008) 9, S.2353-2365 (13 Seiten) PDF als Volltext Verfügbarkeit
Sprache	englisch
Dokumenttyp	gedruckt; online; Zeitschriftenaufsatz
ISSN	0006-8950
DOI	10.1093/brain/awn148
Schlagwörter	Animals; Disabilities; Anatomy; Diseases; Cytology; Role; Brain; Molecular Structure; Diagnostic Tests; Models; Neurology + Suchen Sie Ihr Suchwort? Animal; Tier; Tiere; Handicap; Behinderung; Anatomie; Disease; Krankheit; Zytologie; Rollen; Gehirn; Diagnostic test; Diagnostischer Test; Analogiemodell; Neurologie
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 naive 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 naive OT-I cells "in vitro", and both major histocompatibility complex class I expression and the OT-I response are further up-regulated by interferon-[gamma] (IFN-[gamma]). Release of IFN-[gamma] 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-[gamma] dependent. In conclusion, naive CD8 T-cells gaining access to an "immune-privileged" organ can initiate autoimmunity via an IFN-[gamma]-assisted amplification loop even if the self-antigen in question is not spontaneously released for presentation by professional antigen presenting cells. (As Provided).
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Erfasst von	ERIC (Education Resources Information Center), Washington, DC
Update	2017/4/10