Aberrancies in antigen-presenting cells and T cells in autoimmune thyroid disease. A role in faulty tolerance induction.

Various thyrocyte, monocyte, macrophage, DC and T cell abnormalities exist in the animal models of spontaneously developing autoimmune thyroiditis and in patients with autoimmune thyroid disease. An aberrant interaction between such abnormal thyrocytes, abnormal professional antigen-presenting cells (APC) and abnormal T cells forms the basis for the atypical autoimmune reaction targeting thyroid antigens. In the atypical interaction more than one gene and various environmental factors are involved. The genetic and environmental factors must act together to induce full-blown disease. Although there is a general blueprint for the development of destructive autoimmune thyroiditis, thyrocyte and immune cell abnormalities differ between the various animal models and the various forms of autoimmune thyroid disease (either associated with type 1 diabetes, associated with bipolar disorder or not associated). This tells us that there are different etio-pathogenic forms of destructive autoimmune thyroiditis. Whether such heterogeneity is also the case for the etio-pathogenesis of Graves' disease remains unknown. Animal models of spontaneously developing Graves' disease would be helpful in unraveling this question. If indeed there are various etio-pathogenic routes in different patients that lead to destructive autoimmune thyroiditis, then tailor-made therapeutic approaches need to be carried out in attempts to correct the underlying immune abnormalities in individual patients or to prevent the development of destructive autoimmune thyroiditis in individuals at risk. While in some forms of destructive autoimmune thyroiditis (f.i. those associated with bipolar disorder) immune suppression should be the first choice of intervention, other forms (f.i. those associated with type 1 diabetes) may benefit from immune stimulation in certain pre-stages of the disease (to restore f.i. the faulty APC function characteristic of this condition). Obviously a more precise determination of the spectrum of cell-mediated immune abnormalities is required in individual cases of destructive autoimmune thyroiditis, before therapies that aim at correcting the immune abnormalities can be tested successfully.