Studies of thyroid xenografts from Graves' disease in severe combined immunodeficient mice.

Abstract

Thyroid tissues from normal (paranodular) subjects and patients with Graves' disease (GD) and Hashimoto's thyroiditis (HT) were xenografted to severe combined immunodeficiency (SCID) mice, and the same tissues were engrafted into nude mice; in addition, peripheral blood mononuclear cells were engrafted to separate SCID mice (SCID-PB). Thyroglobulin (TG) and microsomal antibodies (Abs) became detectable with high titers by hemagglutination assays in SCID mice xenografted with thyroid tissues (SCID-TH) from GD and HT patients; moreover, TG Ab was detectable even in SCID-TH from TG Ab-negative GD and HT donors. On the other hand, only 2 of 10 SCID-PB had detectable Abs with low titers. TSH receptor (TSH-R) Ab was detectable in all sets of SCID-TH from GD. After peaking (3-7 weeks), their levels decreased despite the fact that immunoglobulin G levels increased. In addition, in 3 of 4 sets of SCID-PB from GD patients, TSH-R Ab was also detectable. SCID-TH from GD and HT patients showed transient hyperthyroxinemia, peaking at 2 weeks; these values were significantly higher [free T4, 6.48 +/- 0.90 and 5.50 +/- 0.77 pmol/L (mean +/- SE), respectively; P < 0.05] than SCID-TH from normal controls (2.5 +/- 0.24). Histologically, intrathyroidal infiltrating lymphocytes (ITL) survived in SCID mice, but not in nude mice after 8 weeks. The follicles of GD tissue in SCID mice were virtually destroyed with ITL, and their appearance was similar to that in HT. In conclusion, TSH-R Ab was clearly produced from ITL, and some peripheral blood mononuclear cells grafts could also produce TSH-R Ab. In spite of the presence of TSH-R Ab, SCID-TH from GD patients did not show persistent hyperthyroxinemia, presumably because destructive thyroiditis may be occurring in the grafted tissue, with decreasing levels of TSH-R Ab.