IODINE DEFICIENCY INDUCES THYROID AUTOIMMUNE REACTIVITY IN WISTAR RATS

The last 2 decades it has become clear that iodine deficiency has a mo dulating effect on the thyroid autoimmune response in humans. Also, in animals that spontaneously develop autoimmune thyroid disease, eviden ce is accumulating that a low iodine intake can modulate thyroid autoi mmune reactivity. However, it is still not clear what the effect of a low iodine intake on thyroid autoimmune reactivity is in normal nonaut oimmune animals. To study the relationship of a dietary low iodine int ake on the thyroid autoimmune reactivity in nonautoimmune animals, nor mal Wistar rats (female) were kept on an enriched iodine diet (daily i odine intake of 100 mug iodine), a ''for our area normal'' (convention al) diet (COD; daily iodine intake of 7 mug iodine), a low iodine diet (LID; 2 days of 1% KCLO4, followed by iodine-deficient drinking water /pellets), or an extremely low iodine diet (LID+; 1% KCLO4 continuousl y in the drinking water and iodine-deficient pellets). The enriched io dine diet rats were euthyroid (T3, approximately 8 nm/liter; T4, appro ximately 50 nm/liter; TSH, approximately 2 ng/ml), had a normal thyroi d weight (approximately 12.5 mg), and showed only minimal signs of loc al thyroid immune reactivity; low numbers of intrathyroidal dendritic cells (DC; approximately 35 DC/mm2), CD4+ cells (approximately 2 cells /mm2), and CD8+ cells (approximately 2.5 cells/mm2) were found in comb ination with low anticolloid antibody production (incidence of positiv e animals, 12.5%). The COD resulted in a normal thyroid function. The rats were euthyroid (range of T3, 1.6-1.2 nm/liter; T4, approximately 50 nm/liter; TSH, approximately 2 ng/ml) and had a normal thyroid weig ht (approximately 12.5 mg). However, some signs of thyroid autoimmune reactivity were found [number of intrathyroidal DC, approximately 40/M M2; approximately 3 CD4-positive (CD+) cells/mm2; approximately 3 CD8 cells/mm2; together with a 30% incidence of anticolloid antibodies). The LID and LID+ not only induced goiter formation [thyroid weight, 27 .3 +/- 4.2 mg (mean +/- SD) after 12 weeks of LID and 38.4 +/- 5.3 mg after 4 weeks of LID+] and low production of T4 by the thyroid [28 +/- 3 nm/liter (mean +/- SD)] after 12 weeks of LID and 14 +/- 3 nm/liter after 2 weeks of LID+], but also induced various signs of thyroid aut oimmune reactivity. These consisted of. 1) influxes of DC into the thy roid [63.4 +/- 3.8 DC/mm2 (mean +/- SD) after 12 weeks of LID and 64.4 +/- 9.0 DC/mm2 after 3 weeks of LID+]; 2) the formation of homotypic clusters of these DC; 3) influxes of intrathyroidal CD8+ and CD4+ T-ce lls [10.3 +/- 3.5 CD4+ cells/mm2 (mean +/- SD) after 3 weeks of LID, 1 8.0 +/- 4.7 CD4+ cells/mm2 after 4 weeks of LID+, 7.6 +/- 4.1 CD8+ cel ls/mm2 after 6 weeks of LID, and 25.7 +/- 6.3 CD8+ cells/mm2 after 6 w eeks of LID+]; and 4) increases in the production of anticolloid antib odies (incidence of 60% positive animals after 18 weeks of LID and 73% after 10 weeks of LID'). These data, collected from normal nonautoimm une female Wistar rats, show that, as in humans, iodine deficiency pre cipitates thyroid autoimmune reactivity.