Studies on the Mechanism of Tissue Damage in Rat Autoimmune Thyroiditis

In spite of many investigations on experimental autoimmune thyroiditis, the exact relationship between circulating and cellular antibodies and thyroiditis in autoimmunized animals remains to be determined. It seems that it is necessary to make an electron microscopic study of experimental thyroiditis to clarify the precise mechanism of tissue damage, but there has been no report on the ultrastructure of experimental thyroiditis, except for that of Sobel and Geller (1965) On Hashimoto thyroiditis, Irvine and Muir (1963) have recently made an electron microscopic styudy of human chronic thyroiditis and described the presence of the intimate interreaction between invading lymphocytes and the epithelial cells of the thyroid follicles.The present electron microscopic study on rat autoimmune thyroiditis was carried out to reconfirm their observations. In addition, in order to investigate the localization of autoantibody in the thyroid gland to rat autoimmune thyroiditis, the immunoelectron microscopy was used, and the following results were obtained : 1) Electron micrographs of the thyroid gland, taken 8 weeks later, showed a marked expansion and an extensive confluence of the ergastoplasmic sacs, degeneration and tumefaction of mitochondria, nuclear abnormalities, invasion of dense inflammatory cells, distortion and loss of microvilli; and furthermore, in areas of severe cellular necrosis, disruption of plasma membrane or basement membrane of follicular cells appeared. As a very interesting evidence, it was ovserved that tenuous processes of epithelial cells connect intimately with those of invading lymphocytes. This observation, we believe, is in accord with the finding of Irvine and Muir (1963).2) To investigate the results obtained by fluorescent antibody technique also at subcellular level, immunoelectron microscopic studies of thyroiditis were made.First, the result of applying a ferritin conjugate (ferroglobulin) of a globulin fraction of rat serum with severe thyroiditis to the sections of rat thyroid gland with extensive lesions, revealed localization of the antibody in colloid, in ergastoplasmic sacs and on their membranes, and in the perinuclear space.Second, the incubation of the same thyroid tissue sections with a ferritin conjugate of a globulin fraction of rabbit antirat gamma globulin antibody showed localization of ferritin granules (host gamma globulin) in the same regions observed in the first experiment. It was ascertained that ferritin granules (thyroid autoantibody) were also present in the cytoplasm of invading lymphocytes into thyroid follicle. It seems likely that lymphoid cells infiltrating the thyroid gland of rat thyroiditis may be synthesizing globulins -presumably antibody to the thyroid components.These studies have shown that tissue damage in experimental thyroiditis may be mediated by the infiltrating inflammatory cells; especially, the presence of germinal centers may be implicated in the production of autoantibody which reacted damagingly with thyroid constituents in situ, thereby releasing more thyroglobulin, and this in turn may provoke further antibody production (“vicious cycle”). In addition, one can suggest also the possibility that the intimate contact between follicular epithelial cells and invading lymphocytes may allow the direct transfer of lymphocyte-bound thyroid autoantibody to the follicular cells, as described by Irvine and Muir (1963). As Koffler and Friedman (1964) and Koffler and Paronetto (1963) have postulated previously, humoral antibody, especially cytotoxic antibody may be of significance in the pathogenesis of experimental thyroiditis, a synergistic role of serum antibody may also not be excluded.