Exacerbation of autoimmune thyroiditis by a single low dose of whole-body irradiation in non-obese diabetic-H2h4 mice.
OBJECTIVE
To evaluate how irradiation affects thyroid autoimmunity in mouse models of Hashimoto's thyroiditis and Graves' hyperthyroidism.


METHODS
Non-obese diabetic (NOD)-H2(h4) mice spontaneously develop anti-thyroglobulin (Tg) antibodies and thyroiditis when supplied with sodium iodine (NaI) in the drinking water. BALB/c mice develop anti-thyrotropin receptor (TSHR) antibodies and hyperthyroidism following immunization with adenovirus expressing TSHR (Ad-TSHR). Mice were irradiated as follows: A single whole-body irradiation with 0.05, 0.5 or 3 Gy one week before or after the beginning of NaI or immunization with Ad-TSHR, fractionated whole-body irradiations with 0.05 Gy twice a week or 0.5 Gy once a week from one week before NaI or Ad-TSHR immunization, or a single regional irradiation to the thyroid gland with 0.5 Gy one week before NaI. The effect of a single irradiation with 0.05, 0.5 or 3 Gy on splenocytes was also evaluated.


RESULTS
A single whole-body irradiation with 0.5 Gy one week before NaI exacerbated thyroiditis and increased anti-Tg antibody titers in NOD-H2(h4) mice. In contrast, any irradiation protocols employed did not affect incidence of hyperthyroidism or anti-TSHR antibody titers in BALB/c mice. High-dose irradiation increased the relative ratios of effector T cells to regulatory T cells (an indication of enhanced immune status) but kills most of T cells.


CONCLUSIONS
These results indicate that a single whole-body low-dose irradiation with 0.5 Gy exacerbates thyroiditis in NOD-H2(h4) mice, data consistent with some clinical evidence for increased incidence of thyroid autoimmunity by environmental irradiation.
Nagayama
Yuji
Y
Department of Medical Gene Technology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. nagayama@nagasaki-u.ac.jp
Kaminoda
Kazuhisa
K
Mizutori
Yumiko
Y
Saitoh
Ohki
O
Abiru
Norio
N
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000906:Antibodies / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D015967:Gene Expression Regulation, Viral; D006111:Graves Disease / Q000276:immunology / Q000473:pathology; D006183:H-2 Antigens / Q000276:immunology*; D050031:Hashimoto Disease / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D006801:Humans; D007114:Immunization; D051379:Mice; D016688:Mice, Inbred NOD; D011829:Radiation Dosage; D011989:Receptors, Thyrotropin / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000528:radiation effects; D013967:Thyroiditis, Autoimmune / Q000276:immunology / Q000473:pathology*; D014916:Whole-Body Irradiation
D000906:Antibodies; D006183:H-2 Antigens; D011989:Receptors, Thyrotropin