ラッテ自己免疫甲状腺炎における組織障害機構の研究

(第1報) 血清学的ならびに組織学的研究

抄録

The presence of thyroid autoantibodies in Hashimoto's disease and experimentally induced thyroiditis in animals makes it seem most possible that the lesions in the thyroid gland result from an autoimmune process. Since Rose and Witebsky (1956) many workers have described now they could induce the autoimmune thyroiditis in the dog, rabbit and guinea pig by immunization with homologous thyroid extract with Freund's adjuvant.
These investigations have had a considerable bearing upon the mechanisms underlying the pathogenesis of Hashimoto's thyroiditis. Mackay et al. described the concept of “autoclasia” that the leak of thyroglobulin, and possibly of other thyroid antigens from its follicle might stimulate the formation of autoantibodies in lymphoid tissue and then damage thyroid constituents in situ, thereby releasing more thyroglobulin : thus chain reaction might ensue, culminating in eventual destruction of the gland, but to clarify this concept further investigations may be required.
In 1961 Jones and Roitt showed that marked thyroiditis could be evoked consistently in the rat by immunization with homologous or heterologous thyroid extract or thyrogloblin in Freund's adjuvant, and that tissue destruction was mediated primarily by the invading inflammatory cells, and serum antibody might be implicated, perhaps in a synergistic role.
Following this lead, Wistar strain rats were injected with homologous thyroid suspensions in complete Freund's adjuvant. The present investigation was made in the course of immunization of rats, using serologic and histologic methods. The results obtained were as follows :
1) Wistar strain rats weighing 200 gm. were immunized by injecting 0.1 ml. of the thyroid emulsion mixed with an equal volume of complete Freund's adjuvant (Difco) intradermally in 2 divided doses in each food pad every two weeks. Four animals given a mixture of Freund's adjuvant and saline only (saline emulsion) served as controls.
2) The thyroid glands were removed at 3, 4, 6 and 8 weeks after immunization and their histologic changes were examined. Three weeks later the initial change appeared consisting of a decrease of colloid and sparse infiltration of inflammatory cells. Six weeks later more advanced damage occurred consisting of dense infiltration of inflammatory cells, disruption of colloid, and desquamation of the lying follicle epithelial cells. Eight weeks later severe damage appeared; there were islet-like follicles due to the distortion of the normal thyroid architecture by dense infiltration of inflammatory cells into the interstitial tissue, the presence of germinal centers and occasionally, the leakage of colloid into the interstitium; and furthermore, the development of fibrosis.
3) Circulating thyroid autoantibodies were measured by Oudin or BDB test. BDB hemagglutinating antibodies showed generally a remarkably higher level, compared with precipitating antibodies. Three weeks later circulating thyroid autoantibodies appeared. BDB antibody reached its maximum level (4096) 8 weeks later, and thereafter decreased gradually. An Ouchterlony test, using purified thyroglobulin and microsomal preparation sshowed the presence of anti-thyroglobulins and anti-microsomal antibodies in the serum of rats with severe thyroiditis.
4) In order to investigate the localization of autoantibody in the thyroid gland of rat autoimmune thyroiditis, the fluorescent antibody technique was used, and the following results were obtained : the result of applying a fluorescent antirat gamma globulin to the frozen section of rat thyroid gland with extensive lesions demonstrated that the fluorescein conjugate was present mainly within the follicles, and sometimes in the cells of the follicular epithelium; the staining pattern of intrafollicular colloid was homogeneous or follicular-type. In addition, specific fluorescence (gamma globulin) was also present in the cytoplasm of inflammatory cells.