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Chickens of the Obese strain (OS) develop a spontaneous, hereditary autoimmune thyroiditis during the first weeks of life which parallels human Hashimoto's thyroiditis in all clinical, histopathological and serological aspects. This review summarizes the results from investigations on this strain with special emphasis on the pathogenic effector mechanisms leading to the autoimmune destruction of the thyroid gland. The fact that this model disease arises in an avian species is particularly advantageous because of the clear-cut anatomical and functional division of the immune system. Data are discussed which suggest the following pathogenesis of spontaneous autoimmune thyroiditis: B cells and their products, i.e. thyroglobulin autoantibodies, play a decisive role in the initial phases of the disease, such antibodies are first vertically transferred from the mother hen via the egg yolk into the embryo and newly hatched chick, the immune system of which then takes over their production. T-helper cells are required for the formation of the thyroglobulin autoantibodies. These antibodies can either be complement-fixing or mediate destruction of the target cells via antibody-dependent cellular cytotoxicity (ADCC). B cells themselves also destroy thyroid epithelial cells directly in ADCC-like fashion. Cytotoxic T cells seem to play a minor role in the beginning, but add to the destruction of the thyroid gland later. The underlying defect appears to be a deficient intrathymic maturation of suppressor cells leading to a lack of their emigration to the periphery. The development of the disease is under multigenic control, involving at least three loci. Genes associated with the B locus [the major histocompatibility complex (MHC) of the chicken] and a non-B locus seem to be responsible for the immunological hyperreactivity of the OS towards autologous (thyroid and non-thyroid) and exogenous antigens. The third locus is considered to determine a primary thyroid defect thus predisposing this organ as a prime target for the manifestation of autoimmune disease in the OS.

In addition to thyroglobulin autoantibodies, some Obese strain (OS) chickens gave organ-specific reactions with the cytoplasm of thyroid acinar cells when the sera were tested by immunofluorescence. The staining pattern was similar to that seen with human antibodies to thyroid microsomes. A proportion stained the proventricular glands of the chicken stomach in a manner indistinguishable from that of pernicious anaemia sera containing parietal cell antibodies. Isolated examples of organ-specific reactions with adrenal and exocrine pancreas were also recorded. These findings strengthen the notion that the OS chicken represents an authentic model for human organ-specific autoimmune disease. The high incidence of non-organ specific reactions complicates but does not necessarily invalidate this view since normal chickens show a propensity to develop such antibodies. However the OS chicken appears to differ from the human in being hyper-responsive to antigens in general.

Chickens of the Obese strain (OS) exhibit a hereditary, spontaneous auto-immune thyroiditis. Thyroglobulin auto-antibodies have so far been demonstrated by passive haemagglutination and precipitation. A standardized indirect immunofluorescent staining system has been established as an additional technique for the demonstration of these antibodies. Two kinds of circulating thyroglobulin antibodies were found in OS chickens, one demonstrable by passive haemagglutination only, the other by both precipitation and indirect immunofluorescence using a fluorescein isothiocyanate conjugate directed predominantly against chicken IgG. Results obtained in chessboard type indirect immunofluorescence blocking tests and with column chromatographic fractions of OS sera are suggestive that the haemagglutinating kind of thyroglobulin antibodies are of the IgM class, while the antibodies reactive in precipitation and indirect immunofluorescence are of IgG type. The autoantibody nature of the thyroglobulin antibodies in OS chickens was demonstrated by indirect and direct immunofluorescent staining of autologous thyroid sections. With the immunofluorescence techniques employed so far, antibodies directed against antigenic components of the thyroid epithelium of OS chickens have not been demonstrated.

The Obese strain of White Leghorn chickens is afflicted with a spontaneously occurring autoimmune thyroiditis. Thyroglobulin auto-antibodies predominate in the sera of Obese strain chickens, but precipitating auto-antibodies against components of other organs—mainly liver and kidney—also occur in a low percentage, either in combination with or in the absence of thyroglobulin antibodies. Surgical bursectomy in ovo or on the day of hatching completely prevents the formation of precipitating non-thyroid antibodies in the Obese strain chickens. On the other hand, neonatal thymectomy results in a significant increase in the incidence of liver and kidney antibodies in Obese strain, and even in normal White Leghorn chickens. Thymo-bursectomy on the day of hatching has an effect similar to that of bursectomy alone, i.e. prevents the appearance of liver and kidney antibodies. Neonatal, sublethal total body X-irradiation also leads to a slightly lower frequency of liver and kidney antibodies in Obese strain chickens. A possible control function of the intact thymus over the self-recognition mechanism is discussed.