**3.5 Apoptosis in GD**

Apoptosis is absolutely essential for the development of the aggressive immune system. The initial theories about thyroidectomy-induced autoimmunity postulated that antibody and T cell-mediated destruction of the thyroid contributed to the death of thyrocytes. In the ensuing years, it is discovered that apoptosis had a part in GD [38]. Apoptosis provided a new insight into autoimmune target destruction, further implying the participation in possible pathogenesis of thyroid autoimmunity from death-controlled receptors and cytokine-related apoptotic pathways. An abnormally increased level of CD4(+) regulatory T cells break host immune tolerance and initiate T-reg apoptosis [39] and, in this way, foster abnormal T-mediated immune activation in patients with GD. Bcl-2 regulatory protein family is recently linked to the pathogenesis of GD [40] looked at apoptotic proteins, and observed a relation to the expression of the Bcl-2 regulatory family in the thyroid follicular cells in GD [41]. Furthermore, the researchers suggested that an increase in apoptotic molecules (Fas/FasL and caspase 8) are present on T and B lymphocytes in GD and HT patients, demonstrating involvement in GD pathogenesis. It is clear to describe in apoptosis, death receptors/ligands play a regulatory role, but caspase-independent mechanisms can also coexist and contribute to GD thyroid cell death.
