Effects of thyroid hormones on apoptotic cell death of human lymphocytes

Apoptosis plays a critical role in the development and homeostasis of tissu es, especially those with high cell turnover such as the lymphoid system. W e have examined the effects of thyroid hormones, TSH and TRH, on apoptosis of human T lymphocytes. We found that T lymphocytes cultured with T-3 and T -4, but not TSH nor TRH, in vitro showed enhanced apoptosis, evidenced by D NA ladder formation and characteristic morphological changes. In addition, prolonged cultivation with thyroid hormones of the lymphocytes further enha nced the extent of apoptosis. We also found that treatment with thyroid hormones of T lymphocytes induced reduction of mitochondrial transmembrane potential (Delta Psi) and product ion of reactive oxygen species, both of which are intimately associated wit h apoptotic cell death. In addition, cellular expression of antiapoptotic B cl-2 protein was clearly reduced by the treatment of lymphocytes with thyro id hormones in vitro. Thus, T lymphocytes treated with thyroid hormones acc ompany reduction of Bcl-2 protein expression, production of reactive oxygen species, and reduction of mitochondrial Delta Psi, resulting in apoptotic lymphocyte death. Moreover, we found that lymphocytes in patients with Grav es' disease showed enhanced apoptosis compared with those in normal individ uals. These results suggest that thyroid hormones have the potential to ind uce apoptotic cell death of human lymphocytes in vivo and in vitro. (J Clin Endotrinol Metab 84: 1378-1385, 1999).