STUDIES OF HUMAN THYROID XENOGRAFTS FROM HASHIMOTOS-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 im munodeficient (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 a ll 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 thy roid grafts was higher than the donors' original level, and was detect able in mice with thyroid grafts from Tg-Ab-negative HT donors. Thyroi d stimulation-blocking antibody (TSBAb) was found in 2 mice with thyro id xenografts from 1 HT patient whose original serum TSBAb and thyrotr opin-binding inhibitor immunoglobulin (TBII) had been positive; the ma ximal TSBAb level in SCID mice exceeded the donor's original level. TS BAb production in SCID mice reached its peak at 10 weeks after xenogra fting, i.e., later than that of thyroid-stimulating antibody (TSAb) ob served in our recent report, suggesting the existence of distinct intr athyroidal B cell autoreactive clones of different life span responsib le for secreting TSAb or TSBAb. When autologous peripheral blood monon uclear cells (PBMC) were engrafted alone (without thyroid tissue), TSB Ab was undetectable. In conclusion, (a) TSBAb was produced in 2 SCID m ice with a thyroid xenograft from 1 TSBAb-positive HT patient but not in autologous PBMC-engrafted SCID mouse, and (b) TSBAb production reac hed its peak at 10 weeks after xenografting, later than that of TSAb, suggesting the existence of distinct intrathyroidal B cell autoreactiv e clones responsible for secreting thyroid antibodies.