Differential Susceptibility of BALB/c and BALB/cBy mice to Graves' hyperthyroidism.

BALB/c mice are susceptible to the induction of Graves' hyperthyroidism. To investigate the susceptibility of BALB/c substrains of mice to the induction of hyperthyroidism, we immunized BALB/cJ and BALB/cByJ mice with an adenovirus expressing amino acid residues 1-289 of thyrotropin receptor (TSHR). The data presented in this article showed that 17 of 26 (65%) BALB/c and only 4 of 30 (13%) BALB/cBy mice developed hyperthyroidism.

Differential requirement of signal transducer and activator of transcription-4 (Stat4) and Stat6 in a thyrotropin receptor-289-adenovirus-induced model of Graves' hyperthyroidism.

T helper type 1 (Th1) and Th2 cells have critical roles in the development of cell-mediated and humoral immune responses, respectively. This division of function predicts that Th1 cells mediate inflammatory diseases and Th2 cells promote antibody (Ab)-mediated autoimmunity. Our previous studies using HEK-293 cells expressing the extracellular domain of the TSH receptor (TSHR) showed that Stat4-/- mice, which lack Th1 cells, are susceptible, whereas Stat6-/- mice, which lack Th2 cells, are resistant to the induction of Graves' hyperthyroidism.

Signal transducer and activator of transcription (Stat)-6-dependent, but not Stat4-dependent, immunity is required for the development of autoimmunity in Graves' hyperthyroidism.

The role of T helper (Th) cells in experimental models of Graves' hyperthyroidism is still somewhat controversial. To further investigate the role of Th1- and Th2-dependent immunity during the development of Graves' hyperthyroidism, we tested mice with targeted deletion of signal transducer and activator of transcription-4 (Stat4) or Stat6 genes that, respectively, have impaired Th1 and Th2 immunity. We immunized wild-type BALB/c, Stat4(-/-), or Stat6(-/-) mice with human embryonic kidney cells (293 cells) expressing the extracellular domain of human TSH receptor (293-TBP cells).