Apoptosis and thyroiditis.

The origin of the various forms of autoimmune thyroiditis remains unclear. Most investigations into the pathogenesis of these disorders have focused on immune abnormalities that might lead to an autoimmune response. However, no unique immune response to thyroid autoantigens has been identified that either is limited to patients with thyroiditis or is absolutely correlated with clinical disease expression. CD8 T-cell-mediated cytotoxicity is thought to be a major cause of thyroid follicular cell damage in thyroiditis. This damage is produced in part through the induction of apoptosis in thyroid cells. Recent studies have demonstrated that programmed cell death is regulated in thyroid cells and that a major pathway for immune-mediated apoptosis, the Fas pathway, is blocked by labile inhibitors in a manner that could prevent cytotoxicity. This review also examines several other types of regulation of apoptotic pathways in thyrocytes. We hypothesize that the regulation of programmed cell death pathways in the thyroid may alter the expression of autoimmune thyroid diseases by modifying the susceptibility of thyroid cells to immune-mediated apoptosis.