| First Author | Sanchez-Ruiz M | Year | 2008 |
| Journal | J Immunol | Volume | 180 |
| Issue | 12 | Pages | 8421-33 |
| PubMed ID | 18523310 | Mgi Jnum | J:137132 |
| Mgi Id | MGI:3798101 | Doi | 10.4049/jimmunol.180.12.8421 |
| Citation | Sanchez-Ruiz M, et al. (2008) Molecular mimicry between neurons and an intracerebral pathogen induces a CD8 T cell-mediated autoimmune disease. J Immunol 180(12):8421-33 |
| abstractText | To identify basic mechanisms of how infections may induce a neuron-specific autoimmune response, we generated mice expressing OVA as neuronal autoantigen under control of the neuron-specific enolase promoter (NSE-OVA mice). Intracerebral, but not systemic, infection with attenuated Listeria monocytogenes-secreting OVA induced an atactic-paretic neurological syndrome in NSE-OVA mice after bacterial clearance from the brain, whereas wild-type mice remained healthy. Immunization with attenuated Listeria monocytogenes-secreting OVA before intracerebral infection strongly increased the number of intracerebral OVA-specific CD8 T cells aggravating neurological disease. T cell depletion and adoptive transfer experiments identified CD8 T cells as decisive mediators of the autoimmune disease. Importantly, NSE-OVA mice having received OVA-specific TCR transgenic CD8 T cells developed an accelerated, more severe, and extended neurological disease. Adoptively transferred pathogenic CD8 T cells specifically homed to OVA-expressing MHC class I(+) neurons and, corresponding to the clinical symptoms, approximately 30% of neurons in the anterior horn of the spinal cord became apoptotic. Thus, molecular mimicry between a pathogen and neurons can induce a CD8 T cell-mediated neurological disease, with its severity being influenced by the frequency of specific CD8 T cells, and its induction, but not its symptomatic phase, requiring the intracerebral presence of the pathogen. |
