STUDIES OF THYROID XENOGRAFTS FROM GRAVES-DISEASE IN SEVERE COMBINED IMMUNODEFICIENT MICE

Thyroid tissues from normal (paranodular) subjects and patients with G raves' 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 mononucle ar cells were engrafted to separate SCID mice (SCID-PB). Thyroglobulin (TG) and microsomal antibodies (Abs) became detectable with high tite rs by hemagglutination assays in SCID mice xenografted with thyroid ti ssues (SCID-TH) from GD and HT patients; moreover, TG Ab was detectabl e even in SCID-TH from TG Ab-negative GD and HT donors. On the other h and, only 2 of 10 SCID-PB had detectable Abs with low titers. TSH rece ptor (TSH-R) Ab was detectable in all sets of SCID-TH from GD. After p eaking (3-7 weeks), their levels decreased despite the fact that immun oglobulin G levels increased. In addition, in 3 of 4 sets of SCID-PB f rom 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 infiltr ating lymphocytes (ITL) survived in SCID mice, but not in nude mice af ter 8 weeks. The follicles of GD tissue in SCID mice were virtually de stroyed with ITL, and their appearance was similar to that in HT. In c onclusion, 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 per sistent hyperthyroxinemia, presumably because destructive thyroiditis may be occurring in the grafted tissue, with decreasing levels of TSH- R Ab.