Iodine Induced Lymphocytic Thyroiditis in the Bb/W Rat: Early and Late Immune Phenomena

Abstract

The effect of iodine excess on thyroid function and on the immunological sequence of events leading to lym-phocytic thyroiditis (LT) was studied in the NB subline of BB/W rats to determine the mechanisms by which the level of iodine intake influences the development of LT in this animal model. Iodine supplemented water (500 μg/l, Group I or 500 mg/l. Group 2) or non-iodine supplemented tap water (Group 3) was given to breeding pairs and their offspring ad libitum. A Wistar rat group, also given tap water (Group 4) served as controls. To determine the immunological sequence of events, the phenotypic nature of the infiltrating thyroid lymphocytes was examined by specific immunoperoxidase staining in BB/W and Wistar rats at 6, 9. 12, and 15 weeks. Antigen-presenting cells and class II (Ia) antigen expression on thyrocytes were also examined.

The first immunological event apparent in the iodine-treated BB/W rats was a sharp increase in the number of la positive dendritic cells at 9 weeks compared with control BB/W and Wistar rats. In the iodine excess groups dendritic cells were associated with scattered areas of lymphocytic infiltration. comprising predominantly T helper cells (W3/25). T suppressor cells (OX 8) and IL-2 receptor positive activated T-cells (OX 39) were both present in small numbers. B:cells (OX 12) were absent. In addition. thyrocytes did not exhibit la antigen expression. By contrast, lymphocytic infiltration was not found at 9 weeks in control BB/W rats. At 12 to 15 weeks, there was not only a marked increase in the number of lymphocytes, but lymphocytes now formed into large aggregates in iodine excess treated BB/W rats. Immunoperoxidase staining showed that although T-helper cells were still the predominant cell type within the lymphocytic aggregates. iodine treatment had resulted in a reduced number of T-helper cells when compared with control BB/W rats. In addition, IL-2 receptor positive activated T cells and B cells were present in the lymphocytic aggregates of the iodine treated rats. Lymphocytic infiltration at this stage was associated with thyroid follicular cell destruction in the high iodine supplemented groups. Class II (Ia) antigen expression on thyrocytes was a late immunological event and only seen on thyrocytes in direct contact with lymphocytic aggregates.

In conclusion, a high iodine intake accelerates the development of lymphocytic thyroiditis in the BB/W rat. Iodine appears to mediate these effects on the immunological process, by initially stimulating antigen-presenling cells and later activated T lymphocytes. la expression on thyrocytes was a late immunological feature, suggesting that it is a consequence rather than an initiating event in this autoimmune process. It is still not clear from the present study whether the initiating effects of iodine on antigen-presenting cells is a direct effect on immune effector cells, or whether it represents a response secondary to a toxic effect of iodine on thyroid subcellular structures.

Key Words:

• Lymphocytic thyroiditis
• dendritic cells
• class II antigen
• iodine excess
• BB/W rat