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

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 Autoimmun

journal_title

Journal of autoimmunity

authors

Badami E,Maiuri L,Quaratino S

doi

10.1016/j.jaut.2005.01.003

subject

Has Abstract

pub_date

2005-03-01 00:00:00

pages

85-91

issue

2

eissn

0896-8411

issn

1095-9157

pii

S0896-8411(05)00004-1

journal_volume

24

pub_type

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