B. E. Wenzel

An in vitro model for thyroid autoimmunity

Clinical observations have suggested an association between iodine intake and the occurance of autoimmune thyroiditis in man (1,2), while in areas with endemic goiter prevalence due to iodine deficiency a lower incident of Hashimoto’s thyroditis was found (3), Others, however, have contested these claims (4,5). Experimentally, this association has been demonstrated with genetically susceptible chicken (6), rats (7) and dogs (8) on a high iodized diet. In the present study, we were interested in the effect iodine would have on the functional immune response of human Tlymphocytes in co-cultures with autologous thyroid epithilial cells (TECs). Classically, only immunocompetent cells, namely macrophages are able to present antigen together with the immunregulatory class-II surface antigen(9)•These class-II antigens (in man HLA-D locii) can also be found in vivo (10) and induced by various agents in vitro(11) on TECs. With this background our in vitro model system was designed to i) modulate HLA-D expression on TECs and ii) to investigate,if a potential iodide induced autoantigen on TECs would be presented through HLA-D to autologous T-lymphocytes and thus initiate a proliferative cellular immunresponse. In order to modulate the hypothetical iodine induced autoantigen the influence of Methimazole (MMI) and perchlorate (PC) on the co-culture system was to be studied. MMI has been suspected to act immune suppressively during suppression therapy of Graves’ disease (GD) in vivo and on antibody synthesis in vitro (12). Interestingly, when MMI therapy in GD hyperthyroidism was compared to PC treatment, which clearly is no immuno suppressive agent, both drugs had the same effect on the production of thyroid stimulating antibodies (TSab) (13).

Thyrotrophin and Growth Promoting Immunoglobulin(TGI) of FRTL-5 Cells Have No Growth Stimulating Activity on Human Thyroid Epithelial Cell Cultures

When growth promoting activity on thyroid cells was discovered in immunoglobulin fractions (TGI) from patients with goitrous Graves’ disease (GD), an intriguing concept to explain goitre formation was created (l). Indeed, TGI-like activity subsequently was described in patients with nontoxic (NTG) or recurrent goitres (2,3,4)- Recently however, some doubts were cast on this concept for goitre formation, since TGI activity could not be found in highly purified IgG fractions and growth promoting activity in IgG fractions prepared by ammonsulfate precipitation was attributed to contaminations with epidermal growth factor (EGF) (5) Moreo v e r, TGI has not yet been convincingly detected with assay systems using human thyroid epithial cells (TEC). Our own interest to reassess TGI activities was triggered by the inability to find TGI in serum from patients with euthyroid or recurrent goitres (not shown). We therefore investigated the growth promoting activities of TGI samples, TSH and EGF on human TEC and on rat FRTL-5 cells. In both assay systems tritriated thymidin ( HTdR) uptake, glucoses- phosphate dehydrogenase (G-6-PD) and adenylcyclase (cAMP) were measured.