De Assis Paiva, Humberto Jorge; (1990) Characterization of the humoral and cellular immune responses to thyroglobulin in rodent models of autoimmune thyroiditis. Doctoral thesis (Ph.D), UCL (University College London).

Text out.pdf Download (16MB)

Abstract

In order to understand the mechanisms underlying autoimmune thyroiditis, spontaneous (SAT) and induced (EAT) autoimmune responses to thyroglobulin were investigated in various inbred strains of rats. The humoral response was assessed using a solid-phase immunoradiometric method and the cell-mediated immunity was evaluated by histology and immunofluorescence analysis. Anti-Tg autoantibodies, spontaneously arising in BB rats (S-TgAb) and induced in various inbred strains of rats (l-TgAb), differed in their fine specificity. With a panel of thyroglobulins from different animal species it was demonstrated that l-TgAb bound to all species of Tg, whereas S-TgAb either recognized a restricted number of Tg-species or all thyroglobulins. Moreover, it was shown that the iodination site of thyroglobulin is the epitope recognized by both spontaneous and induced TgAb. Taken together these data are consistent with the view of restricted epitope recognition by Tg autoantibodies in the rat. Comparing the induction of thyroiditis in a variety of intra-RT.1 recombinant rat strains, it was demonstrated that on identical genetic backgrounds the RT.1c haplotype was directly associated with high and the RT.1u haplotype with low responses to EAT induction. The severity of the induced thyroiditis did not correlate with Tg-autoantibody titres in either strain. The inflammatory infiltrate was essentially composed of macrophages and T lymphocytes in both spontaneous and induced rat thyroiditis models. However, in the SAT of the BB/E rat a substantial number of B lymphocytes was also present in the infiltrates. Immunoglobulin deposition was seen in the thyroid interstitium and in damaged follicles in both EAT and SAT. MHC Class II was expressed on the thyroid epithelium in EAT but not SAT and was observed only in areas of massive lymphocytic infiltration. Furthermore, interferon-gamma induced class II expression on a rat thyroid epithelial cell line (FRTL-5) in vitro. In the non obese diabetic mouse protocols for induction of thyroiditis and tolerization were standardized. Preliminary data indicate that induction of thyroiditis by immunization with Tg can be abrogated by prior i. v. injection of a high dose of Tg. These findings strongly suggest a central pathogenic role for T cell-dependent mechanisms, although antibody-mediated cytotoxicity cannot be ruled out. They support the notion that thyroid epithelial class II MHC antigen expression is a secondary event in the pathogenesis of rat EAT, mediated through cytokines released by activated cells in the inflammatory infiltrate.

Download activity - last month

Export as JSONCSVXML

Download activity - last 12 months

Export as CSVXMLJSON

Downloads by country - last 12 months

Export as JSONXMLCSV

Archive Staff Only

View Item