A novel myelin P0-specific T cell receptor transgenic mouse develops a fulminant autoimmune peripheral neuropathy.
Autor(es): Louvet Cédric; Kabre Beniwende G.; Davini Dan W.; Martinier Nicolas; Su Maureen A.; DeVoss Jason J.; Rosenthal Wendy L.; Anderson Mark S.; Bour-Jordan Hélène; Bluestone Jeffrey A.
Resumo: 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.
Imprenta: The Journal of Experimental Medicine, v. 206, n. 3, p. 507-514, 2009
Identificador do objeto digital: 10.1084/jem.20082113
Descritores: Guillain-Barre Syndrome - Biosynthesis ; Guillain-Barre Syndrome - Cell ; Guillain-Barre Syndrome - Cytopathology ; Guillain-Barre Syndrome - Pathogenesis ; Guillain-Barre Syndrome - Protein synthesis ; Guillain-Barre Syndrome - Proteins ; Guillain-Barre Syndrome - Cytokines ; Guillain-Barre Syndrome - Immunology
Data de publicação: 2009