Induction of a TC1-mediated experimental autoimmune thyroiditis by deglycosylated porcine thyroglobulin.

Contribution of cytotoxic T lymphocytes (CTL) to experimental autoimmune thyroiditis (EAT) was well defined (Speidel et al., Eur. J. Immunol. 1997, 27, 2391-2399, Ref. 7). The native porcine thyroglobulin (pTg) showed high sensitivity to endo-o-N-acetylglucosaminidase F (Endo F) and its molecular weights, corresponding to about 330 kDa as a monomer and 660 kDa as a dimer, were reduced to smaller molecular weight forms by Endo F and trifluoromethanesulfonic acid (TMSF). Deglycosylated porcine Tg (dgpTg) and native pTg were injected i.v. into CBA/J mice, without the aid of adjuvants. Both lymphocytic infiltrations of the thyroid glands and levels of Tg-specific CTL were similar to those found in conventional EAT induced by Tg and adjuvants. In contrast, proliferative responses in native pTg and dgpTg-injected mice could not be detected, and titers of antibodies to pTg and dgpTg were 20 times and 30 times lower than that of pTg and adjuvants, respectively. The EAT-inducer CTL belonged to the CD8+ cell subset and exerted their thyroiditogenic potential through release of IFN-gamma. It was concluded that dgpTg-induced EAT is mediated by type 1 cytotoxic T cells (Tcl). Also, results that EAT induction of the glycosylated pTg (gpTg) was much lower than that of dgpTg, suggested that the abberant and incomplete glycosylation of the thyroglobulin is responsible for the induction of autoimmune thyroiditis.

Effect of herbal medicines on cytokine-induced cytotoxicity and major histocompatibility complex (MHC) class II antigen expression in rat thyroid cells.

The effects of herbal medicines that constitute Gam-du-tang and Gung-gui-tang on cytokine-induced cytotoxicity and thyroid major histocompatibility complex (MHC) class II antigen expression in FRTL rat thyrocytes were investigated. No effect on cell growth was found with interferon (IFN)-gamma. However, tumor necrosis factor (TNF)-alpha was cytotoxic, and this was increased by preincubation with IFN-gamma. Ethanol extract of Glycyrrhizae Radix, black beans, Angelicae Radix, and Cnidii Rhizoma (0.3-15 mg/ml) in both regimens significantly inhibited IFN-gamma and TNF-alpha-mediated cytotoxicity of rat thyroid cells (p<0.05, p<0.01). In addition, IFN-gamma (1-100 U/ml) treatment induced class II antigen expression in up to 60% of FRTL cells, as detected by a murine monoclonal antibody to rat MHC class II antigen (FITC-OX6). Aberrant thyroid cell MHC class II antigen expression induced by IFN-gamma is suppressed by the extract of herbal medicines. These results indicate that herbal medicines inhibit cytokine-induced thyroid cell destruction, therefore, may have therapeutic potential in the treatment of autoimmune thyroid disease.