IODINE-INDUCED LYMPHOCYTIC THYROIDITIS IN THE BB W RAT - EARLY AND LATE IMMUNE PHENOMENA/

The effect of iodine excess on thyroid function and on the immunologic al sequence of events leading to lymphocytic thyroiditis (LT) was stud ied in the NB subline of BB/W rats to determine the mechanisms by whic h the level of iodine intake influences the development of LT in this animal model. Iodine supplemented water (500 mug/l, Group 1 or 500 mgA , Group 2) or non-iodine supplemented tap water (Group 3) was given to breeding pairs and their offspring ad libitum. A Wistar rat group, al so given tap water (Group 4) served as controls. To determine the immu nological sequence of events, the phenotypic nature of the infiltratin g thyroid lymphocytes was examined by specific immunoperoxidase staini ng in BB/W and Wistar rats at 6, 9, 12, and 15 weeks. Antigen-presenti ng 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 Ia positive dendritic cells at 9 weeks compared with control BB/W and Wistar rats. In the i odine excess groups dendritic cells were associated with scattered are as of lymphocytic infiltration, comprising predominantly T helper cell s (W3/25). T suppressor cells (OX 8) and IL-2 receptor positive activa ted T-cells (OX 39) were both present in small numbers. B-cells (OX 12 ) were absent. In addition, thyrocytes did not exhibit Ia antigen expr ession. 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 predomina nt cell type within the lymphocytic aggregates, iodine treatment had r esulted in a reduced number of T-helper cells when compared with contr ol BB/W rats. In addition, IL-2 receptor positive activated T cells an d B cells were present in the lymphocytic aggregates of the iodine tre ated rats. Lymphocytic infiltration at this stage was associated with thyroid follicular cell destruction in the high iodine supplemented gr oups. Class II (Ia) antigen expression on thyrocytes was a late immuno logical event and only seen on thyrocytes in direct contact with lymph ocytic aggregates. In conclusion, a high iodine intake accelerates the development of lymphocytic thyroiditis in the BB/W rat. Iodine appear s to mediate these effects on the immunological process, by initially stimulating antigen-presenting cells and later activated T lymphocytes . la expression on thyrocytes was a late immunological feature, sugges ting that it is a consequence rather than an initiating event in this autoimmune process. It is still not clear from the present study wheth er the initiating effects of iodine on antigen-presenting cells is a d irect effect on immune effector cells, or whether it represents a resp onse secondary to a toxic effect of iodine on thyroid subcellular stru ctures.