Länger F, Rippegather K, Caspar G, Herrmann G, Usadel K H, Schumm-Draeger P M
Senckenbergisches Zentrum der Pathologie, Johann Wolfgang Goethe-Universität, Frankfurt a. M.
Verh Dtsch Ges Pathol. 1996;80:303-7.
In this study we investigated the functional and morphological properties of xenotransplanted human thyroid tissue in nude mice following systemic application of intrathyroidal lymphocyte preparations from patients with Graves' disease (GD) and non-toxic nodular goiter (NTG). Thyroid tissue samples from 17 NTG-patients were transplanted into athymic nude mice for a period of 4-5 weeks. Aliquots of lymphocyte preparations from both peripheral blood samples (PBL) and thyroid tissue (ITL) of 13 patients with GD and 12 patients with NTG were analyzed by flow-cytometry (CD3, CD4, CD8, CD56) and injected (i.v.) into transplanted nude mice. Animals injected with saline solution served as a control. After 48 h transplants were harvested and histological (H&E) as well as immunohistological evaluation was performed (MHCII, IgG, IgM). Control animals and mice treated with both PBL and ITL from NTG patients showed regular thyroid tissue without lymphocytic infiltrates or local expression of human immunoglobulins. Application of PBL and ITL of GD patients caused scant to moderate lymphocytic infiltrates with detection of human immunoglobulin production. Injection of GD-ITL was accompanied by a significantly higher proportion of intrathyroidal CD3+ lymphocytes and MHCII expression of adjacent thyroid epithelium as compared to injection of GD-PBL preparations. Our results demonstrate that GD-lymphocytes of both peripheral but especially intrathyroidal origin migrate specifically to human thyroid transplants in the nude mouse model, survive for at least two days, secrete immunoglobulins and induce MHCII expression.
在本研究中,我们调查了将格雷夫斯病(GD)和非毒性结节性甲状腺肿(NTG)患者的甲状腺内淋巴细胞制剂全身应用于裸鼠体内后,异种移植的人甲状腺组织的功能和形态学特性。将17例NTG患者的甲状腺组织样本移植到无胸腺裸鼠体内4 - 5周。通过流式细胞术(CD3、CD4、CD8、CD56)分析13例GD患者和12例NTG患者外周血样本(PBL)及甲状腺组织(ITL)中的淋巴细胞制剂等分试样,并静脉注射到移植后的裸鼠体内。注射盐溶液的动物作为对照。48小时后收获移植组织,进行组织学(苏木精和伊红染色)及免疫组织学评估(MHCII、IgG、IgM)。对照动物以及用NTG患者的PBL和ITL处理的小鼠显示甲状腺组织正常,无淋巴细胞浸润或人免疫球蛋白的局部表达。应用GD患者的PBL和ITL导致少量至中度淋巴细胞浸润,并检测到人免疫球蛋白产生。与注射GD - PBL制剂相比,注射GD - ITL伴随着甲状腺内CD3 +淋巴细胞比例显著更高以及相邻甲状腺上皮的MHCII表达。我们的结果表明,外周来源尤其是甲状腺内来源的GD淋巴细胞在裸鼠模型中特异性迁移至人甲状腺移植组织,存活至少两天,分泌免疫球蛋白并诱导MHCII表达。