A novel myelin P0-specific T cell receptor transgenic mouse develops a fulminant autoimmune peripheral neuropathy

作者：Louvet Cedric; Kabre Beniwende G; Davini Dan W; Martinier Nicolas; Su Maureen A; DeVoss Jason J; Rosenthal Wendy L; Anderson Mark S; Bour Jordan Helene; Bluestone Jeffrey A^*

来源：Journal of Experimental Medicine, 2009, 206(3): 507-514.

DOI：10.1084/jem.20082113

The Journal of Experimental Medicine 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-Barre 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.

• 出版日期2009-3-16