Spontaneous autoimmune thyroiditis in NOD.H-2h4 mice

Abstract

NOD.H-2h4 mice, which express I-Ak on the NOD genetic background, spontaneously develop autoimmune thyroiditis (SAT) and anti-mouse thyroglobulin (MTg) autoantibodies. The incidence of SAT is nearly 100% in mice of both sexes 6-8 weeks after administration of 0.05% NaI in the drinking water. After reaching maximum severity, inflammation is chronic over the next 3-4 months. All mice that develop thyroid lesions also produce MTg-specific IgG1 and IgG2b autoantibodies. Thyroid lesions and anti-MTg autoantibodies did not develop in CBA/J (H-2(k)) or NOD.SWR(H-2(q)) mice after administration of NaI water. Both CD4(+)and CD8(+)T cells are involved in the initial development of SAT. Depletion of CD4(+), but not CD8(+), T cells after thyroid lesions have developed also markedly reduced SAT severity, indicating that CD4(+)T cells are required for both developing and maintaining SAT. Analysis of cytokine gene expression indicated that both Th1 and Th2 cytokines were expressed in thyroids of NOD.H-2h4 mice with SAT. Th1 and proinflammatory cytokines were maximally expressed 4-6 weeks after mice began receiving NaI water, while Th2 cytokine gene expression was greatest at 8-15 weeks, when lesions had reached maximal severity and were in the chronic phase. TGF-beta was highly expressed in NOD.H-2h4 thyroids, irrespective of whether the mice had received NaI water or had thyroid lesions.