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Effects of Thyroid Hormones on Apoptotic Cell Death of Human Lymphocytes¹

Departments of Immunology and Medicine (S.M., N.S., S.W., T.H., T.S.) and Internal Medicine (S.W., S.S., N.Se., N.Sa.), St. Marianna University School of Medicine, Kawasaki, Kanagawa; and the Department of Dermatology, Hiroshima University School of Medicine (S.M., S.Y.), Hiroshima, Japan

Address all correspondence and requests for reprints to: Dr. Tsuyoshi Sakane, Departments of Immunology and Medicine, St. Marianna University School of Medicine, 2–16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan.

Apoptosis plays a critical role in the development and homeostasis of tissues, especially those with high cell turnover such as the lymphoid system. We have examined the effects of thyroid hormones, TSH and TRH, on apoptosis of human T lymphocytes. We found that T lymphocytes cultured with T₃ and T₄, but not TSH nor TRH, in vitro showed enhanced apoptosis, evidenced by DNA ladder formation and characteristic morphological changes. In addition, prolonged cultivation with thyroid hormones of the lymphocytes further enhanced the extent of apoptosis.

We also found that treatment with thyroid hormones of T lymphocytes induced reduction of mitochondrial transmembrane potential () and production of reactive oxygen species, both of which are intimately associated with apoptotic cell death. In addition, cellular expression of antiapoptotic Bcl-2 protein was clearly reduced by the treatment of lymphocytes with thyroid hormones in vitro. Thus, T lymphocytes treated with thyroid hormones accompany reduction of Bcl-2 protein expression, production of reactive oxygen species, and reduction of mitochondrial , resulting in apoptotic lymphocyte death. Moreover, we found that lymphocytes in patients with Graves’ disease showed enhanced apoptosis compared with those in normal individuals. These results suggest that thyroid hormones have the potential to induce apoptotic cell death of human lymphocytes in vivo and in vitro.

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