ovalbumin and Brain-Diseases

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.

Topics: Adoptive Transfer; Animals; Autoantigens; Brain Diseases; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Differentiation; Chickens; Humans; Listeria monocytogenes; Listeriosis; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular Mimicry; Nervous System Autoimmune Disease, Experimental; Neurons; Ovalbumin; Phosphopyruvate Hydratase; Promoter Regions, Genetic; Rats

Topics: Anaphylaxis; Animals; Brain Diseases; Cerebral Ventricles; Female; Injections, Intraventricular; Ovalbumin; Rats; Rats, Inbred Strains