We generated a novel double transgenic (Tg) mouse model on the naturally diabetes resistant C57Bl/6 background, co-expressing two transgenes including a specific TCR anti-lymphocytic choriomeningitis virus nucleoprotein (LCMV-NP) carried by CD8<sup>+</sup> T cells and LCMV-NP (as neo-self antigen) expressed by pancreatic beta cells.
We have found that RAGE is expressed intracellularly in human T cells following TCR activation but constitutively on T cells from patients with diabetes.
To study the immune tolerance and regulatory environment permissive for such autoreactive T cells, we expressed TCR transgenes derived from two autoreactive human T cells, 4.13 and 164, in HLA-DR4 transgenic mice on a C57BL/6-derived "diabetes-resistant" background.