Immunological events leading to destructive thyroiditis in the AUG rat

Abstract

Single or infrequent observations in patients or animals with autoimmune thyroid disease (AITD) have failed to elucidate the exact sequence of pathogenetic events leading to thyroid cell destruction. A detailed serial morphological and functional study of experimental AITD (EAITD) in the female AUG rat was therefore undertaken. Following induction of EAITD with thyroglobulin (Tg) in adjuvant antibodies to Tg were detectable one week after the initial immunization, at which stage Ia positive vascular endothelium was observed within the thyroid. This was followed by large numbers of Ia positive dendritic-like cells. With time, in almost all the animals whose titre of Tg antibody rose above a critical level, lymphocytic infiltration was observed consisting mainly of Ia positive B cell aggregates with fewer scattered T cells. This was associated with raised levels of serum TSH and concomitant focal follicular hyperplasia and necrosis. Expression of Ia was mainly restricted to the outer epithelial wall of follicular thyrocytes in direct contact with invading lymphoid cells, although occasional staining on the internal apical membrane was observed as a late event in the destructive process. The Ia expression on thyroid epithelial cells was only observed in areas of thyroid lymphoid infiltration. The immune infiltration of the thyroid in the AUG rat appears to be very similar to that observed in Hashimoto's thyroiditis, with the exception that Ia was not regularly observed on the apical surfaces of thyrocytes. Whether or not the diminished or absent epithelial Ia expression contributes to the spontaneous recovery of the disease observed in this model remains to be resolved.