| First Author | Louvet C | Year | 2009 |
| Journal | J Exp Med | Volume | 206 |
| Issue | 3 | Pages | 507-14 |
| PubMed ID | 19221395 | Mgi Jnum | J:146797 |
| Mgi Id | MGI:3838455 | Doi | 10.1084/jem.20082113 |
| Citation | Louvet C, et al. (2009) A novel myelin P0-specific T cell receptor transgenic mouse develops a fulminant autoimmune peripheral neuropathy. J Exp Med 206(3):507-14 |
| abstractText | 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. |
