**7. Pathogenesis**

The activation of CD4 T-lymphocytes specic for thyroid antigens is believed to be the rst step in pathogenesis. Once activated, self-reactive CD4 T cells recruit cytotoxic CD8 T cells as well as autoreactive B cells into the thyroid. T cells play a crucial role in disease pathogenesis by reacting with thyroid antigens and secreting inflammatory cytokines. Besides the others, mutations in the Tg gene and CTLA-4 are associated with HT (31,32). The three main targets of thyroid antibodies are Tg, TPO, and the TSH receptor. It is

believed that these autoantibodies are secondary to thyroid follicular cell damage induced by T cells Anti-TPO antibodies have been shown to inhibit the activity of the enzyme in vitro, but direct cytotoxicity by CD8 T cells is believed to be the main mechanism of hypothyroidism in vivo. Thyroid peroxidase is the major autoantigen and autoantibodies to TPO are closely associated with disease activity. Although this has not been proven in children Anti-TSH receptor antibodies of the blocking type may contribute to hypothyroidism in a minority of adult patients with the atrophic form of autoimmune thyroiditis. Histologically, HT is characterized by diffuse lymphocytic inltration with occasional germinal centers. Thyroid follicles may be reduced in size and contain sparse colloid. Individual thyroid cells are often enlarged with oxyphilic cytoplasm. In contrast, the gland of atrophic autoimmune thyroiditis is small, with lymphocytic inltration and brous replacement of the parenchyma (5).
