Studies of Human Thyroid Xenografts from Hashimoto's Thyroiditis in Severe Combined Immunodeficient (SCID) Mice: Detection of Thyroid Stimulation-Blocking Antibody

Human thyroid xenografts from 7 patients with Hashimoto's thyroiditis (HT) and 3 normal persons (N) were xenografted into severe combined immunodeficient (SCID) mice to study the intrathyroidal lymphocytes that were expected to survive in these animals. Human IgG was detected in all mice engrafted with HT thyroid tissue peaking at 6–10 weeks after xenografting. Thyroperoxidase-antibody (TPO-Ab) was also detected in all mice with HT thyroid grafts peaking at 4–6 weeks after xenografting, reaching up to 44% of donors' original concentrations. In contrast, maximal thyroglobulin (Tg)-Ab production in some SCID mice with HT thyroid grafts was higher than the donors' original level, and was detectable in mice with thyroid grafts from Tg-Ab-negative HT donors. Thyroid stimulation-blocking antibody (TSBAb) was found in 2 mice with thyroid xenografts from 1 HT patient whose original serum TSBAb and thyrotropin-binding inhibitor immunoglobulin (TBII) had been positive; the maximal TSBAb level in SCID mice exceeded the donor's original level. TSBAb production in SCID mice reached its peak at 10 weeks after xenografting, i.e., later than that of thyroid-stimulating antibody (TSAb) observed in our recent report, suggesting the existence of distinct intrathyroidal B cell autoreactive clones of different life span responsible for secreting TSAb or TSBAb. When autologous peripheral blood mononuclear cells (PBMC) were engrafted alone (without thyroid tissue), TSBAb was undetectable. In conclusion, (a) TSBAb was produced in 2 SCID mice with a thyroid xenograft from 1 TSBAb-positive HT patient but not in autologous PBMC-engrafted SCID mouse, and (b) TSBAb production reached its peak at 10 weeks after xenografting, later than that of TSAb, suggesting the existence of distinct intrathyroidal B cell autoreactive clones responsible for secreting thyroid antibodies.