|Budget Amount *help
¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1990 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1989 : ¥1,200,000 (Direct Cost : ¥1,200,000)
To elucidate the specificities of autoimmune response to thyroglobulin (Tg) in murine autoimmune thyroiditis, we studied antigen specific proliferative response to Tg in good and poor responder mice and experimental autoimmune thyroiditis (EAT) induced by immunization with Tg or Tg fragments. Mouse and human Tg digested with staphylococcal V8 protease were separated into 8 mouse Tg fractions (Frl-Fr8 : 470kDa-8kDa) and 7 human Tg fractions (Frl-Fr7 : 470kDa-14kDa) by high performance liquid chromatography. The results obtained are as follows :
1. Lymphocytes from CBA mice proliferated in response to both Tg and Tg Fr, when mice were immunized with mouse Tg. In contrast, B10 or BALB/c lymphocytes primed with mouse Tg did not proliferate detectably in response to mouse Tg but proliferated in response to some mouse Tg Fr. In addition, when BALB/c mice were immunized with mouse Tg Fr 4 instead of Tg, proliferative response to mouse Tg as well as Tg Fr developed in these mice. These data indicate that T cells capable of responding to Tg exist in BALB/c mice, although they are low responder strain to Tg. Immune response to Tg in low responder mice might be suppressed by regulatory cells.
2. EAT was induced by immunization with mouse Tg Fr1-Fr5 (470kDa-35kDa) in B6C3F1 mice, whereas EAT was hardly induced by immunization with mouse Tg Fr with molecular weight smaller than 18kDa. When B6C3F1 mice were immunized with human Tg Fr1-Fr6 (470kDa-18kDa), EAT was also induced in them. In addition, immunization, immunization with bovine Tg, human Tg as well as mouse Tg induced thyroiditis in mice. These findings suggest that restricted antigenic determinants of Tg, including interspecies cross-reactive Tg antigenic determinants, are related to thyroiditis.