A novel myelin P0-specific T cell receptor transgenic mouse develops a fulminant autoimmune peripheral neuropathy
| Autor: | Beniwende Kabre, Maureen A. Su, Hélène Bour-Jordan, Dan Davini, Cedric Louvet, Wendy Rosenthal, Nicolas Martinier, Jason DeVoss, Mark S. Anderson, Jeffrey A. Bluestone |
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| Rok vydání: | 2009 |
| Předmět: |
CD4-Positive T-Lymphocytes
Receptors Antigen T-Cell alpha-beta Neurodegenerative Medical and Health Sciences Transgenic Myelin Interleukin 21 Mice Epitopes 0302 clinical medicine Mice Inbred NOD Receptors Immunology and Allergy Cytotoxic T cell 2.1 Biological and endogenous factors IL-2 receptor Aetiology alpha-beta 0303 health sciences FOXP3 Peripheral Nervous System Diseases 3. Good health medicine.anatomical_structure Phenotype Antigen Neurological Cytokines Myelin P0 Protein T cell Immunology Mice Transgenic Biology Autoimmune Disease Recombination-activating gene Autoimmune Diseases 03 medical and health sciences medicine Animals Peripheral Nerves Peripheral Neuropathy 030304 developmental biology Cell Proliferation Hybridomas Inflammatory and immune system Brief Definitive Report Neurosciences T-Cell Brain Disorders Inbred NOD 030217 neurology & neurosurgery |
| Zdroj: | The Journal of experimental medicine, vol 206, iss 3 The Journal of Experimental Medicine |
| Popis: | 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 γ 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. |
| Databáze: | OpenAIRE |
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