Autoimmune thyroid disease--a perspective.
Increasing evidence is accruing in favour of the view that autoimmune thyroid disease is due to an organ-specific defect in suppressor T lymphocytes that is genetically induced. While the initial evidence supporting this hypothesis was based on results with the migration inhibition factor test, subsequent investigations from our own and other laboratories have confirmed the presence of such an organ-specific suppressor T lymphocyte defect in autoimmune thyroid disease. Moreover, there is now good evidence that hyperthyroidism per se has an effect on suppressor T lymphocyte function and numbers, and this is superimposed on and is additive to the organ-specific defect while patients are hyperthyroid; this may well act as a self-perpetuating factor in continuing the disease. It has been proposed elsewhere that the expression of HLA-DR antigen on the cell membrane of the thyrocytes (possibly induced by viral infection) represents the initial inductive step in precipitating autoimmune thyroid disease in persons predisposed by virtue of having an immunoregulatory defect in the first place. However, there is now evidence that: (1) normal thyrocytes respond equally well to various stimuli in terms of DR expression when compared to Graves' or Hashimoto's thyrocytes; (2) supernatants from normal T lymphocytes will stimulate DR expression on thyrocytes at least as well as supernatants from Graves' T lymphocytes when stimulated by non-specific lectins; (3) conversely, Graves' T lymphocytes will stimulate thyroid DR expression more markedly than normal T lymphocytes when the lymphocyte-thyrocyte interaction is direct; (4) monocytes and helper T lymphocytes are essential for thyrocyte DR expression; (5) DR expression on thyrocytes does not lead to a self-perpetuating immune response. From all of these observations, it seems evident that DR expression is secondary to the primary immune assault in autoimmune thyroid disease, and is neither an initiating event, nor unique to autoimmune thyroid disease, nor a self-perpetuating phenomenon.
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D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001665:Binding Sites; D005802:Genes, MHC Class II; D006111:Graves Disease / Q000235:genetics / Q000276:immunology*; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D018828:Immunoglobulins, Thyroid-Stimulating; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D011989:Receptors, Thyrotropin; D013601:T-Lymphocytes / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000235:genetics / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D018828:Immunoglobulins, Thyroid-Stimulating; D011956:Receptors, Cell Surface; D011989:Receptors, Thyrotropin