Yoshikawa N, Arreaza G, Mukuta T, Resetkova E, Miller N, Jamieson C, Volpé R
Endocrinology Research Laboratory, Wellesley Hospital, University of Toronto, ON, Canada.
Thyroid. 1994 Spring;4(1):13-8. doi: 10.1089/thy.1994.4.13.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
将7例桥本甲状腺炎（HT）患者和3例正常人（N）的人甲状腺异种移植到严重联合免疫缺陷（SCID）小鼠体内，以研究预期能在这些动物体内存活的甲状腺内淋巴细胞。在所有移植了HT甲状腺组织的小鼠中均检测到人类IgG，在异种移植后6 - 10周达到峰值。在所有移植了HT甲状腺移植物的小鼠中也检测到甲状腺过氧化物酶抗体（TPO - Ab），在异种移植后4 - 6周达到峰值，高达供体原始浓度的44%。相比之下，一些移植了HT甲状腺移植物的SCID小鼠中甲状腺球蛋白（Tg）- Ab的最大产量高于供体原始水平，并且在来自Tg - Ab阴性HT供体的甲状腺移植物的小鼠中也可检测到。在1例HT患者的甲状腺异种移植小鼠中发现了甲状腺刺激阻断抗体（TSBAb），该患者原始血清TSBAb和促甲状腺素结合抑制免疫球蛋白（TBII）呈阳性；SCID小鼠中的最大TSBAb水平超过了供体原始水平。SCID小鼠中TSBAb的产生在异种移植后10周达到峰值，即晚于我们最近报告中观察到的甲状腺刺激抗体（TSAb），这表明存在不同寿命的独特甲状腺内B细胞自身反应性克隆，负责分泌TSAb或TSBAb。当单独移植自体外周血单个核细胞（PBMC）（无甲状腺组织）时，未检测到TSBAb。（摘要截断于250字）
