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

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.

Pubmed ID: 19221395


  • Louvet C
  • Kabre BG
  • Davini DW
  • Martinier N
  • Su MA
  • DeVoss JJ
  • Rosenthal WL
  • Anderson MS
  • Bour-Jordan H
  • Bluestone JA


The Journal of experimental medicine

Publication Data

March 16, 2009

Associated Grants

  • Agency: NIAID NIH HHS, Id: K08 AI076429
  • Agency: NIAID NIH HHS, Id: K08 AI076429-02
  • Agency: NIAID NIH HHS, Id: R01 AI50834

Mesh Terms

  • Animals
  • Autoimmune Diseases
  • CD4-Positive T-Lymphocytes
  • Cell Proliferation
  • Cytokines
  • Epitopes
  • Hybridomas
  • Mice
  • Mice, Inbred NOD
  • Mice, Transgenic
  • Myelin P0 Protein
  • Peripheral Nerves
  • Peripheral Nervous System Diseases
  • Phenotype
  • Receptors, Antigen, T-Cell, alpha-beta