The pathogenicity of spontaneously-occurring thyroglobulin-reactive T lymphocytes from BB/WOR rats

Autoantigen-reactive T lymphocytes have been implicated in the pathogenesis organ-specific autoimmune disease. Thyroglobulin (Tg) is one of the primary autoantigens associated with autoimmune lymphocytic thyroiditis (LT). These experiments investigated the pathogenicity of a lymphocyte line derived from spontaneously-occurring Tg-reactive T lymphocytes isolated from unprimed NB line BB/Wor rats which have nearly a 100% incidence of spontaneous LT. Adoptive transfer of LT was accomplished by injecting 1.0 x 10(5) Tg-reactive lymphocytes into the tail vein of MHC compatible, non LT-prone BB line BB/Wor rats. All of the Tg-reactive cell line recipients (5/5) developed LT compared to only 20% (1/5) of the control rats given a parallel tetanus toxoid-reactive T cell line (p < 0.05, Fisher's exact test). Furthermore, despite the presence of LT, only one Tg-reactive cell line recipient developed insulitis. When Tg-reactive lymphocytes were incubated with an MHC compatible Wistar rat thyrocyte line at increasing effector: target ratios, the T cell line lysed thyrocytes in a dose-response fashion (r = 0.99, p < 0.05, linear regression), but did not lyse smooth muscle cell targets. FACS analysis established that this cell line is CD8 predominant. This is the first study to demonstrate that spontaneously-occurring Tg-reactive T lymphocytes from a nonimmunized animal model for LT are pathogenic. Further investigations into the repertoire of Tg-reactive lymphocytes in BB/Wor rats should provide insight into the pathogenesis of autoimmune thyroid disease and provide a basis for targeted immunotherapy.