| First Author | Na SY | Year | 2008 |
| Journal | Brain | Volume | 131 |
| Issue | Pt 9 | Pages | 2353-65 |
| PubMed ID | 18669487 | Mgi Jnum | J:337408 |
| Mgi Id | MGI:7494399 | Doi | 10.1093/brain/awn148 |
| Citation | Na SY, et al. (2008) Naive CD8 T-cells initiate spontaneous autoimmunity to a sequestered model antigen of the central nervous system. Brain 131(Pt 9):2353-65 |
| abstractText | 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. |
