Soliman M, Kaplan E, Straus F, Fisfalen M E, Hidaka Y, Guimaraes V, DeGroot L J
Department of Medicine, University of Chicago, Illinois 60637, USA.
J Clin Endocrinol Metab. 1995 Oct;80(10):2848-55. doi: 10.1210/jcem.80.10.7559863.
Graves' disease (GD) is an autoimmune thyroid disorder involving an antibody (TSAb) directed against the TSH receptor (TSHR) producing thyroid stimulation. We have developed an animal model of GD by engrafting peripheral blood mononuclear cells or T cell lines plus autologous thyroid tissue into severe combined immunodeficient (SCID) mice. We xenografted Graves' thyroid tissue from six patients into six groups of SCID mice. Autologous PBMC and T cell lines reactive to recombinant human TSHR extracellular domain and non-TSHR lines were injected ip into the designated groups. In some of the studies, thyroid tissue was irradiated with 2000 rads before xenografting. Irradiation of xenografts induced thyroid tissue damage and release of thyroid antigens and hormones. Mice reconstituted with peripheral blood mononuclear cells or nonspecific T cell lines did not simulate GD. However, we achieved production of TSAb, elevation of serum T3, and TSAb-dependent survival and function of human Graves' thyroid tissue in SCID mice reconstituted with TSHR-specific T cell lines. We reconstituted SCID mice with PBMC and TSHR-specific T cell lines that recognized TSHR peptide 158-176. This may be in vivo evidence of the importance of peptide 158-176 as an immunodominant epitope on the TSHR extracellular domain.
格雷夫斯病（GD）是一种自身免疫性甲状腺疾病，涉及一种针对促甲状腺激素受体（TSHR）的抗体（TSAb），可产生甲状腺刺激作用。我们通过将外周血单个核细胞或T细胞系与自体甲状腺组织移植到严重联合免疫缺陷（SCID）小鼠体内，建立了GD动物模型。我们将6例患者的格雷夫斯甲状腺组织异种移植到6组SCID小鼠体内。将对重组人TSHR细胞外结构域有反应的自体PBMC和T细胞系以及非TSHR细胞系腹腔注射到指定组中。在一些研究中，甲状腺组织在异种移植前接受2000拉德的照射。异种移植的照射导致甲状腺组织损伤以及甲状腺抗原和激素的释放。用外周血单个核细胞或非特异性T细胞系重建的小鼠并未模拟出GD。然而，在用TSHR特异性T细胞系重建的SCID小鼠中，我们实现了TSAb的产生、血清T3的升高以及人格雷夫斯甲状腺组织依赖TSAb的存活和功能。我们用识别TSHR肽158 - 176的PBMC和TSHR特异性T细胞系重建了SCID小鼠。这可能是肽158 - 176作为TSHR细胞外结构域上免疫显性表位重要性的体内证据。
