Autoimmunity causing thyroid dysfunction

Considerable evidence for a genetically induced antigen-specific defect in suppressor T lymphocytes as the basis for AITD has been derived from several laboratories and via different types of experimental techniques. This defect may result from abnormal antigen presentation to T lymphocytes via an aberrant antigen-specific HLA-related gene. In addition, there is now evidence for additive effects on reducing generalized suppressor T lymphocyte numbers and function by environmental factors as well as hyperthyroidism itself. These effects would be superimposed on the organ-specific defect. Such effects on generalized suppressor T lymphocyte numbers may act as precipitating and self-perpetuating factors. Presentation of the antigen by the thyroid cell via HLA-DR expression on its cell membrane does occur as a result of IFN-gamma production by T lymphocytes. This appears to be secondary to the initial specific immune assault and is not a primary inductive step. Although it may be important as an amplifying intermediate factor, antigen presentation cannot perpetuate the process in the absence of the underlying immune disorder. There is, indeed, no evidence for an underlying antigenic abnormality or stimulus in human autoimmune thyroid disease, and the initiating event would appear to be due to perturbation of the generalized immune system superimposed on the organ-specific immunoregulatory abnormality. Variations in the serologic and clinical expression of AITD would appear to depend on the severity of the original organ-specific disturbance in suppressor T lymphocyte function, plus the added factor of environmental influences playing on generalized suppressor T lymphocyte function and numbers. Remissions in Graves' disease brought about by antithyroid drugs may well be via their effect on modulating thyroid cell activity; this then reduces thyrocyte-immunocyte signaling, allowing remission to occur in those patients with a partial organ-specific defect in suppressor T lymphocytes.