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| Article Authors: | Cédric Louvet; Beniwende G Kabre; Dan W Davini; Nicolas Martinier; Maureen A Su; Jason J DeVoss; Wendy L Rosenthal; Mark S Anderson; Hélène Bour-Jordan; Jeffrey A Bluestone |
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| Article Title: | A novel myelin P0-specific T cell receptor transgenic mouse develops a fulminant autoimmune peripheral neuropathy. |
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| Reference ID: | 1014233 |
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| Abstract: | Autoimmune-prone nonobese diabetic mice deficient for B7-2 spontaneously develop an autoimmune peripheral neuropathy mediated by inflammatory CD4(+) T cells that is reminiscent of Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy. To determine the etiology of this disease, CD4(+) T cell hybridomas were generated from inflamed tissue-derived CD4(+) T cells. A majority of T cell hybridomas were specific for myelin protein 0 (P0), which was the principal target of autoantibody responses targeting nerve proteins. To determine whether P0-specific T cell responses were sufficient to mediate disease, we generated a novel myelin P0-specific T cell receptor transgenic (POT) mouse. POT T cells were not tolerized or deleted during thymic development and proliferated in response to P0 in vitro. Importantly, when bred onto a recombination activating gene knockout background, POT mice developed a fulminant form of peripheral neuropathy that affected all mice by weaning age and led to their premature death by 3-5 wk of age. This abrupt disease was associated with the production of interferon gamma by P0-specific T cells and a lack of CD4(+) Foxp3(+) regulatory T cells. Collectively, our data suggest that myelin P0 is a major autoantigen in autoimmune peripheral neuropathy. |
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| Affiliations: | Diabetes Center and the Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. |
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| Date: | 2009 |
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| Reference Type: | Literature |
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| PubMed ID: | 19221395 |
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| Journal: | J Exp Med |
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| Journal Volume: | 206 |
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| Article Pages: | 507-14 |
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| Journal ISSN: | 1540-9538 |
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| Article Chemical List: | Cytokines;Epitopes;Myelin P0 Protein;Receptors, Antigen, T-Cell, alpha-beta |
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| Article MeSH List: | Animals; Autoimmune Diseases(complications; immunology; pathology); CD4-Positive T-Lymphocytes(immunology); Cell Proliferation; Cytokines(biosynthesis); Epitopes; Hybridomas; Mice; Mice, Inbred NOD; Mice, Transgenic; Myelin P0 Protein(metabolism); Peripheral Nerves(immunology; pathology); Peripheral Nervous System Diseases(complications; immunology; pathology); Phenotype; Receptors, Antigen, T-Cell, alpha-beta(immunology) |
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| Curation Last Updated: | 2013-05-28 21:39:15 |
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