Cellular infiltration in induced rat thyroiditis: phenotypic analysis and relationship to genetic restriction.

We have investigated the responsiveness to thyroglobulin (Tg) plus complete Freund's adjuvant (CFA) and B. pertussis in a variety of inbred and MHC congenic strains of rats in terms of both Tg-autoantibody titres and histological thyroiditis index. Severity of thyroiditis was strongly Tg-dependent and closely related to the RT.1-MHC haplotype. Phenotypic examination of the inflammatory thyroid infiltrate using single and double indirect immunofluorescence techniques revealed a high proportion of macrophages and T lymphocytes, mainly of the cytotoxic/suppressor subset, in the high responder strains. Thyroid epithelial class II MHC expression although not prominent was strain-restricted and related to the amount of Ia+ leukocyte infiltrate.

Epitope specificity of spontaneous and induced thyroglobulin autoantibodies in the rat.

We have investigated the epitope specificities of rat thyroglobulin (Tg) autoantibodies arising either spontaneously in BB hybrid and BB rats or following induction in normal rats with thyroglobulin and adjuvant. Using a panel of thyroglobulins from different animal species it was possible to identify three different patterns of reactivity. These were: 1) recognition of all species of thyroglobulin; (2) recognition restricted to rat and mouse thyroglobulins and 3) recognition biased towards dog, rat and mouse thyroglobulins. Furthermore, using human thyroglobulin manifesting different levels of iodination, it was possible to show that sera with recognition pattern 1 recognized the iodination site of thyroglobulin and that this was inhibitable by thyroxine. Taken together these data provide evidence of restricted epitope recognition by Tg autoantibodies in the rat.

Interferon-mediated enhancement of thyroid major histocompatibility complex antigen expression. A flow cytometric analysis.

Epithelial expression of class II antigens encoded by the major histocompatibility complex (MHC) has been proposed as a means by which autoimmune thyroid disease may be initiated and maintained. We studied a rat thyroid epithelial cell line (FRTL-5), which constitutively expresses class I (OX18) but not class II (OX6 or OX17) determinants to quantify in vitro MHC antigen induction using flow cytometry. Recombinant rat gamma interferon (rIFN-gamma) induced dose-dependent expression of OX6 (I-A) antigen at greater than 48 h (maximum 80-90% of cells in culture at 100 U/ml), which was abrogated by DB-1, a monoclonal antibody to rat IFN-gamma. OX17 antigen (I-E) was also induced (86%) and OX18 (class I) markedly increased under these conditions. Other thyroid-active agents including the calcium ionophore A23187, dibutyryl cyclic AMP, thyroid-stimulating autoantibodies from Graves' disease patients (LATS), and TSH, caused no I-A induction. Supernatants from spleen cells stimulated with plant lectins (concanavalin A or phytohaemagglutinin), but not lectin alone, evoked substantial class II induction, which was inhibited by DB-1. These findings suggest that IFN-gamma is the central mediator of thyroid epithelial class II expression. FRTL-5 provides a powerful model for the analysis of thyroid MHC class II dynamics and a potential means of analysing the role of epithelial class II in autoimmune pathogenesis.