Volpé R
Mol Biol Med. 1986 Feb;3(1):25-51.
Increasing evidence is accruing in favour of the view that autoimmune thyroid disease is due to an organ-specific defect in suppressor T lymphocytes that is genetically induced. While the initial evidence supporting this hypothesis was based on results with the migration inhibition factor test, subsequent investigations from our own and other laboratories have confirmed the presence of such an organ-specific suppressor T lymphocyte defect in autoimmune thyroid disease. Moreover, there is now good evidence that hyperthyroidism per se has an effect on suppressor T lymphocyte function and numbers, and this is superimposed on and is additive to the organ-specific defect while patients are hyperthyroid; this may well act as a self-perpetuating factor in continuing the disease. It has been proposed elsewhere that the expression of HLA-DR antigen on the cell membrane of the thyrocytes (possibly induced by viral infection) represents the initial inductive step in precipitating autoimmune thyroid disease in persons predisposed by virtue of having an immunoregulatory defect in the first place. However, there is now evidence that: (1) normal thyrocytes respond equally well to various stimuli in terms of DR expression when compared to Graves' or Hashimoto's thyrocytes; (2) supernatants from normal T lymphocytes will stimulate DR expression on thyrocytes at least as well as supernatants from Graves' T lymphocytes when stimulated by non-specific lectins; (3) conversely, Graves' T lymphocytes will stimulate thyroid DR expression more markedly than normal T lymphocytes when the lymphocyte-thyrocyte interaction is direct; (4) monocytes and helper T lymphocytes are essential for thyrocyte DR expression; (5) DR expression on thyrocytes does not lead to a self-perpetuating immune response. From all of these observations, it seems evident that DR expression is secondary to the primary immune assault in autoimmune thyroid disease, and is neither an initiating event, nor unique to autoimmune thyroid disease, nor a self-perpetuating phenomenon.
越来越多的证据支持这样一种观点，即自身免疫性甲状腺疾病是由遗传诱导的抑制性T淋巴细胞的器官特异性缺陷所致。虽然最初支持这一假说的证据基于迁移抑制因子试验的结果，但我们自己以及其他实验室随后的研究证实，自身免疫性甲状腺疾病中存在这种器官特异性抑制性T淋巴细胞缺陷。此外，现在有充分的证据表明，甲状腺功能亢进本身会对抑制性T淋巴细胞的功能和数量产生影响，在患者甲状腺功能亢进时，这种影响叠加在器官特异性缺陷之上且具有累加性；这很可能是疾病持续存在的一个自我延续因素。其他地方有人提出，甲状腺细胞细胞膜上HLA - DR抗原的表达（可能由病毒感染诱导）是使原本因免疫调节缺陷而易感的人发生自身免疫性甲状腺疾病的初始诱导步骤。然而，现在有证据表明：（1）与格雷夫斯病或桥本甲状腺炎的甲状腺细胞相比，正常甲状腺细胞在DR表达方面对各种刺激的反应同样良好；（2）当受到非特异性凝集素刺激时，正常T淋巴细胞的上清液刺激甲状腺细胞DR表达的效果至少与格雷夫斯病T淋巴细胞的上清液一样好；（3）相反，当淋巴细胞与甲状腺细胞直接相互作用时，格雷夫斯病T淋巴细胞刺激甲状腺DR表达的作用比正常T淋巴细胞更明显；（4）单核细胞和辅助性T淋巴细胞对甲状腺细胞DR表达至关重要；（5）甲状腺细胞上的DR表达不会导致自我延续的免疫反应。从所有这些观察结果来看，很明显DR表达是自身免疫性甲状腺疾病原发性免疫攻击的继发结果，既不是起始事件，也不是自身免疫性甲状腺疾病所特有的，更不是一种自我延续现象。
