Abstract:
: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+CD25hi 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.
journal_name
J Autoimmunjournal_title
Journal of autoimmunityauthors
Badami E,Maiuri L,Quaratino Sdoi
10.1016/j.jaut.2005.01.003subject
Has Abstractpub_date
2005-03-01 00:00:00pages
85-91issue
2eissn
0896-8411issn
1095-9157pii
S0896-8411(05)00004-1journal_volume
24pub_type
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