A Thyroxine-containing Thyroglobulin Peptide Induces both Lymphocytic and Granulomatous Forms of Experimental Autoimmune Thyroiditis

Abstract

Mouse thyroglobulin (MTg)-sensitized spleen cells activated in vitro with MTg can induce two histologically distinct forms of experimental autoimmune thyroiditis (EAT). MTg-sensitized cells activated with MTg alone induce a mild chronic form of EAT in which the thyroid infiltrate consists primarily of lymphocytes and other mononuclear cells (lymphocytic EAT). The same donor cells activated with MTg and anti-IL2R mAb induce a more severe and acute form of EAT with a thyroid inflammatory lesion having granulomatous histopathological features. A thyroxine-containing (T4) peptide, corresponding to positions 2549–2560 of human Tg, was shown by others to activate spleen cells of mouse thyroglobulin (MTg)-sensitized CBA/J mice to induce lymphocytic EAT. To determine if the CD4+effector T cells that induce granulomatous EAT can respond to the same T-cell epitope, the present study was undertaken to determine if both forms of EAT could be induced by the 2549–2560 thyroxine (T4)-containing peptide. This peptide was very effective for activation of T cells from MTg-primed CBA/J donors to induce granulomatous EAT but, in contrast to MTg, did not activate T cells from AKR/J or DBA/1 mice to induce granulomatous EAT. The T4 peptide did not apparently activate peptide-specific B cells in vivo but did activate MTg-primed B cells in vitro to produce anti-MTg autoantibody in recipient mice. These results demonstrate that a single 12-amino-acid thyroxine-containing peptide can activate T cells from CBA/J mice to induce both lymphocytic and granulo-matous EAT. However, this peptide does not activate T cells from some other EAT-susceptible strains of mice, suggesting that MTg contains multiple epitopes able to activate T cells to induce granulomatous EAT.