Miya K, Itoh J, Okagawa K, Kosaka M, Saito S
First Department of Internal Medicine, School of Medicine, University of Tokushima, Japan.
Nihon Naibunpi Gakkai Zasshi. 1987 Oct 20;63(10):1278-88. doi: 10.1507/endocrine1927.63.10_1278.
Anti-thyroglobulin antibody (aTg) synthesis by the lymphocytes in the peripheral blood and the thyroid gland were studied in patients with Hashimoto's disease (HD) or Graves' disease (GD), all in euthyroid states, to clarify the mechanism of autoantibody synthesis. The ability of the lymphocytes to synthesize aTg was analyzed in the culture system of lymphocytes incubated in a concentration of 1 X 10(6) cells/ml for 7 days at 37 degrees C in 5% CO2-95% air. The B cells alone were also cultured in the absence of T cells or PWM to estimate their abilities on spontaneous aTg synthesis. The regulatory functions of T cells on aTg synthesis by B cells were investigated in cross-combination cultures of B cells and an equal number of T cells. The concentration of aTg and total IgG in cultured medium were measured by sensitive enzyme immunoassay developed by us, and the capacity on aTg synthesis was expressed as aTg/IgG ratio (aTg%). The surface markers of lymphocytes in the peripheral blood and the thyroid gland were determined by flowcytometry using mouse monoclonal antibodies (CD3, CD4, CD8, OKIa1, CD20 and Leu7). These results were obtained as follows: 1) All the lymphocytes from the peripheral blood, thyroid gland and bone marrow of HD patients synthesized much more aTg (3.1 +/- 1.6, 2.2 +/- 0.9, 1.5 +/- 0.5%, respectively) than those from normal peripheral blood lymphocytes (1.0 +/- 0.9%). This hyper-function of aTg synthesis by the lymphocytes in HD patients was caused by the presence of activated B cells and the predominance of helper T cells. 2) Both the lymphocytes from the peripheral blood and the thyroid gland in GD patients synthesized the same level of aTg (0.7 +/- 0.7%) as in normal subjects. However, the lymphocytes from bone marrow and lymph nodes, which were indicated by Benner et al. to play a main role in antibody synthesis after immunization with antigen, were involved in aTg synthesis (1.8 +/- 1.2, 5.4 +/- 1.1%, respectively). 3) There was no correlation between aTg synthesis and CD4+/CD8+ ratio of the peripheral blood lymphocytes in AITD patients. These results suggest that aTg synthesis in HD patients is an expression of abnormal immune reaction due to the presence of aTg specific activated B cells and dysfunction of regulatory T cells, and that aTg production by the lymphocytes from the bone marrow and lymph nodes in GD patients is resulted from a normal immune response to the high level of thyroglobulin in the blood.(ABSTRACT TRUNCATED AT 400 WORDS)
为阐明自身抗体合成机制，对处于甲状腺功能正常状态的桥本氏病（HD）或格雷夫斯病（GD）患者外周血及甲状腺中的淋巴细胞合成抗甲状腺球蛋白抗体（aTg）的情况进行了研究。在淋巴细胞培养体系中分析淋巴细胞合成aTg的能力，将淋巴细胞以1×10⁶个细胞/ml的浓度在37℃、5%二氧化碳 - 95%空气环境中培养7天。还在无T细胞或PWM的情况下单独培养B细胞，以评估其自发合成aTg的能力。在B细胞与等量T细胞的交叉组合培养中研究T细胞对B细胞合成aTg的调节功能。采用我们开发的灵敏酶免疫测定法测量培养基中aTg和总IgG的浓度，aTg合成能力以aTg/IgG比值（aTg%）表示。使用小鼠单克隆抗体（CD3、CD4、CD8、OKIa1、CD20和Leu7）通过流式细胞术测定外周血和甲状腺中淋巴细胞的表面标志物。结果如下：1）HD患者外周血、甲状腺及骨髓中的所有淋巴细胞合成的aTg（分别为3.1±1.6%、2.2±0.9%、1.5±0.5%）比正常外周血淋巴细胞（1.0±0.9%）多得多。HD患者淋巴细胞aTg合成功能亢进是由活化B细胞的存在及辅助性T细胞占优势所致。2）GD患者外周血和甲状腺中的淋巴细胞合成的aTg水平（0.7±0.7%）与正常受试者相同。然而，Benner等人指出在抗原免疫后在抗体合成中起主要作用的骨髓和淋巴结中的淋巴细胞参与了aTg合成（分别为1.8±1.2%、5.4±1.1%）。3）AITD患者外周血淋巴细胞的aTg合成与CD4⁺/CD8⁺比值之间无相关性。这些结果表明，HD患者中aTg的合成是由于存在aTg特异性活化B细胞及调节性T细胞功能障碍导致的异常免疫反应的表现，而GD患者骨髓和淋巴结中的淋巴细胞产生aTg是对血液中高水平甲状腺球蛋白的正常免疫反应的结果。（摘要截取自400字）
