Al-Ansari Farah, Lahooti Hooshang, Stokes Leanne, Edirimanne Senarath, Wall Jack
a Department of Academic Medicine , Sydney Medical School, Nepean, The University of Sydney , Kingswood , Australia.
b Department of Endocrinology, Nepean Hospital , Nepean Blue Mountains Local Health District , Kingswood , NSW , Australia.
Endocr Res. 2018 Nov;43(4):264-274. doi: 10.1080/07435800.2018.1470639. Epub 2018 May 22.
Purpose/aim of the study: Graves' ophthalmopathy (GO) is closely related to the thyroid autoimmune disorder Graves' disease. Previous studies have suggested roles for thyroidal CD8 T cells and autoimmunity against calsequestrin-1 (CASQ)-1 in the link between thyroidal and orbital autoimmune reactions in GO. A role for autoimmunity against CollXIII has also been suggested. In this study, we aimed to investigate correlations between some thyroidal and peripheral blood T-cell subsets and thyroidal T-cell reactivity against CASQ1 and CollXIII in patients with GO.
Fresh thyroid tissues were processed by enzyme digestion and density gradient to isolate mononuclear cells (MNCs). Peripheral blood MNCs were also isolated using density gradient. Flow-cytometric analysis was used to identify the various T-cell subsets. T -cell reactivity to CASQ1 and CollXIII was measured by a 5-day culture of the MNCs and BrdU uptake method.
We found a positive correlation between thyroidal CD8 T cells and CD8 T-regulatory (T-reg) cells in patients with GO. Thyroidal T cells from two out of the three patients with GO tested (66.7%) showed a positive response to CASQ1, while thyroidal T cells from none of the six Graves' Disease patients without ophthalmopathy (GD) tested showed a positive response to this antigen. Thyroidal T cells from these patient groups however, showed no significant differences in their response to CollXIII.
Our observations provide further evidence for a possible role of thyroidal CD8 T cells, CD8 T-reg cells and the autoantigen CASQ1 in the link between thyroidal and orbital autoimmune reactions of GO.
研究目的:格雷夫斯眼病(GO)与甲状腺自身免疫性疾病格雷夫斯病密切相关。先前的研究表明,甲状腺CD8 T细胞以及针对肌集钙蛋白-1(CASQ)-1的自身免疫在GO的甲状腺和眼眶自身免疫反应之间的联系中发挥作用。也有人提出针对Ⅻ型胶原(CollXIII)的自身免疫作用。在本研究中,我们旨在调查GO患者中一些甲状腺和外周血T细胞亚群之间的相关性,以及甲状腺T细胞对CASQ1和CollXIII的反应性。
通过酶消化和密度梯度法处理新鲜甲状腺组织以分离单核细胞(MNCs)。也使用密度梯度法分离外周血MNCs。采用流式细胞术分析来鉴定各种T细胞亚群。通过MNCs的5天培养和BrdU摄取法测量T细胞对CASQ1和CollXIII的反应性。
我们发现GO患者的甲状腺CD8 T细胞与CD8调节性(T-reg)细胞之间存在正相关。在检测的3例GO患者中有2例(66.7%)的甲状腺T细胞对CASQ1呈阳性反应,而在检测的6例无眼病的格雷夫斯病(GD)患者中,其甲状腺T细胞对该抗原均无阳性反应。然而,这些患者组的甲状腺T细胞对CollXIII的反应无显著差异。
我们的观察结果为甲状腺CD8 T细胞、CD8 T-reg细胞和自身抗原CASQ1在GO的甲状腺和眼眶自身免疫反应之间的联系中可能发挥的作用提供了进一步的证据。