Yue S J, Enomoto T, Matsumoto Y, Kawai K, Volpé R
Endocrinology Research Laboratory, Wellesley Hospital Research Foundation, University of Toronto, Ontario, Canada.
Thyroid. 1998 Sep;8(9):755-63. doi: 10.1089/thy.1998.8.755.
It has been proposed elsewhere that thyrocyte (TEC) class I expression plays a central role in the pathogenesis of autoimmune thyroid disease (AITD). We have studied thyroid xenografts from patients with Graves' disease (GD) and normal (paranodular) (N) tissues in nude and severe combined immunodeficient (SCID) mice. TEC class I and II expression are markedly increased in GD, as compared with N thyroids. When these tissues are transplanted to nude mice in which the immune environment is deleted from the thyroid grafts, TEC class I and class II expression decline to low levels; interferon-gamma (IFN-gamma) but not interferon-alpha (IFN-alpha) will then upregulate TEC class I and class II expression in these N and GD nude xenografts. In SCID mouse xenografts, GD tissue shows higher TEC class I and II expression compared with N. In these SCID mice, both IFN-alpha and IFN-gamma will stimulate TEC class I and II expression further in both GD and N. However, only IFN-alpha increases thyroid antibody (TAb) production from GD SCID grafts, whereas IFN-gamma causes a rise in GD TEC class I and II expression, but no significant increase in TAb. Moreover, in N SCID grafts, despite a rise in TEC class I and II expression induced by both IFNs, no TAb could be detected. Because an immune environment is necessary for TEC class I and II upregulated expression, we conclude that such upregulation is a secondary phenomenon. Because there was dissociation between the stimulation of TEC class I and II expression versus the production of TAb, then at least under these experimental conditions, there is no support for a role for TEC class I and class II upregulation in the pathogenesis of AITD.
其他地方有人提出，甲状腺细胞（TEC）I类分子的表达在自身免疫性甲状腺疾病（AITD）的发病机制中起核心作用。我们研究了来自格雷夫斯病（GD）患者的甲状腺异种移植物以及正常（结节旁）（N）组织在裸鼠和严重联合免疫缺陷（SCID）小鼠中的情况。与N甲状腺相比，GD中TEC I类和II类分子的表达明显增加。当将这些组织移植到甲状腺移植物中免疫环境缺失的裸鼠体内时，TEC I类和II类分子的表达会降至低水平；此时，干扰素-γ（IFN-γ）而非干扰素-α（IFN-α）会上调这些N和GD裸鼠异种移植物中TEC I类和II类分子的表达。在SCID小鼠异种移植物中，与N相比，GD组织显示出更高的TEC I类和II类分子表达。在这些SCID小鼠中，IFN-α和IFN-γ都会进一步刺激GD和N中的TEC I类和II类分子表达。然而，只有IFN-α会增加GD SCID移植物中甲状腺抗体（TAb）的产生，而IFN-γ会导致GD中TEC I类和II类分子表达升高，但TAb没有显著增加。此外，在N SCID移植物中，尽管两种干扰素都诱导了TEC I类和II类分子表达升高，但未检测到TAb。由于免疫环境对于TEC I类和II类分子上调表达是必要的，我们得出结论，这种上调是一种继发现象。因为TEC I类和II类分子表达的刺激与TAb的产生之间存在分离，所以至少在这些实验条件下，不支持TEC I类和II类分子上调在AITD发病机制中起作用。
