Thyroid autoimmune disorders comprise more than 30% of all organ-specific autoimmune diseases and are characterized by autoantibodies and infiltrating T cells. The pathologic role of infiltrating T cells is not well defined. To address this issue, we generated transgenic mice expressing a human T-cell receptor derived from the thyroid-infiltrating T cell of a patient with thyroiditis and specific for a cryptic epitope of thyroid-peroxidase. This humanized transgenic mouse model (TAZ10) spontaneously developed destructive thyroiditis with clinical, histological and hormonal signs comparable with human autoimmune hypothyroidism. We have therefore shown the pathogenic role of human T cells specific for cryptic self epitopes in the initiation and progression of autoimmune thyroiditis, even in absence of B cells and autoantibodies. Spontaneous autoimmune thyroiditis might also arise in the TAZ10 transgenic mice even in presence of significant amounts of functionally active regulatory T cells and we will discuss how this suppressor mechanism may fail in autoimmunity.