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.