Suppression in experimental autoimmune thyroiditis: the role of unique and shared determinants on mouse thyroglobulin in self-tolerance.

Previous studies have shown that T cells from mice genetically susceptible to experimental autoimmune thyroiditis (EAT) recognize determinants shared between mouse thyroglobulin (Tg) and heterologous Tgs. Some shared determinants are thyroiditogenic; lymphocytes from mice immunized with mouse Tg (MTg) or human Tg (HTg) and reciprocally restimulated in vitro with either Tg can transfer EAT. Studies on the mechanisms of self-tolerance have shown that pretreatment with soluble MTg suppresses in vitro proliferation to MTg and EAT induction with MTg. To determine the role of share epitopes in maintaining tolerance, mice were pretreated with soluble HTg and immunized with HTg or MTg and adjuvant. Cells from HTg-pretreated. HTg-immunized mice showed suppressed in vitro proliferative response to HTg. Following MTg immunization, the cells showed suppressed in vitro response to MTg. However, in contrast to MTg pretreatment, the subsequent development of EAT in vivo was unaltered in severity following HTg pretreatment. Thus, determinants shared between HTg and MTg can induce suppression of in vitro responses to HTg and MTg, but not inhibit the onset of thyroiditis, suggesting that T cells recognizing MTg-unique epitopes expanded to mediate thyroiditis. We conclude that recognition of both unique epitopes expanded to mediate thyroiditis. We conclude that recognition of both unique and shared epitopes on MTg are essential for the overall maintenance of self-tolerance.