Induction of experimental autoimmune thyroiditis (EAT) by heat-denaturated thyroglobulin (Tg)

Experimental Autoimmune Thyroiditis (EAT) is characterized by autoreactive T and B cell responses, assessed by a marked lymphocytic infiltration of the thyroid gland by T cells and the occurrence of circulating autoantibodies (AAb) to thyroglobulin (Tg). It was recently reported that administration of denaturated exogenous antigens primes class I-restricted cytotoxic T cells in vivo. Since cytotoxic T cells are involved in EAT development, porcine Tg (pTg) was heat-denaturated, i.v. injected into CBA/J mice and features of EAT evaluated. Simultaneously, mice were immunized with pTg and adjuvants and evaluation of EAT performed. We found that heat-denaturated pTg (hdpTg) induced EAT in recipient mice similar to native pTg/adjuvants. Surprisingly, whereas Tg-specific cytotoxic T cells were regularly found in lymph node cells from hdpTg or native pTg immunized mice, proliferative responses were only detected using T cells from native pTg immunized mice. Autoantibodies to pTg were decreased by a factor 30 in sera from mice immunized with hdpTg. These data further emphasized the role of Tg-specific cytotoxic T cells in EAT.