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Publication : High incidence of spontaneous autoimmune thyroiditis in immunocompetent self-reactive human T cell receptor transgenic mice.

First Author  Badami E Year  2005
Journal  J Autoimmun Volume  24
Issue  2 Pages  85-91
PubMed ID  15829400 Mgi Jnum  J:97544
Mgi Id  MGI:3575620 Doi  10.1016/j.jaut.2005.01.003
Citation  Badami E, et al. (2005) High incidence of spontaneous autoimmune thyroiditis in immunocompetent self-reactive human T cell receptor transgenic mice. J Autoimmun 24(2):85-91
abstractText  Autoantigen-specific TCR transgenic mice allow us to assess the role of T cells in autoimmunity. We have recently generated humanized TAZ10 transgenic mice expressing the human TCR specific for the immunodominant epitope of thyroid peroxidase (TPO). We have shown that these transgenic mice do not undergo tolerance in vivo and that on Rag deficient background they are susceptible to spontaneous autoimmune thyroiditis. Here we show that, in contrast to other transgenic models of autoimmunity, almost all TCR(+)Rag1(+) (T+R+) T cells are activated in vivo leading to the development of spontaneous autoimmune thyroiditis. In these mice, disease is also accompanied by a significant reduction of CD4+CD25(hi) regulatory T cells. These data indicate that the pathogenic activity of the self-reactive TCR can circumvent the regulatory function operated by the non-transgenic T cells that are normally present in T+R+ mice, leading to autoimmunity.
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