Liakata E, Philippou G, Souvatzoglou A, Lymberi P, Carayanniotis G
Immunology Laboratory, Department of Biochemistry, Hellenic Pasteur Institute, Athens, Greece.
Thyroid. 2003 Jul;13(7):631-6. doi: 10.1089/105072503322239961.
A salient feature of Hashimoto's thyroiditis (HT) is the T-cell-mediated destruction of the thyroid gland leading to hypothyroidism. In HT, as in other autoimmune diseases, a central premise has been that autoreactive T cells must be dividing in response to autoantigens, accumulating random spontaneous mutations during the activation process. Here, we have examined this hypothesis by using as monitor of somatic cell mutation the hprt gene, encoding the salvage pathway enzyme hypoxanthine-guanine phosphoribosyl transferase. Eleven newly diagnosed patients with HT and 10 patients with chronic disease were selected for the study, whereas 10 healthy individuals were used as controls. Peripheral T cells were cultured under limiting dilution conditions in the presence of 6-thioguanine and the frequency (MF) of surviving mutant hprt(-) T cells was calculated by Poisson statistics. It was observed that the mean MF value of either patient group (6.6 +/- 5.8 per 10(6) cells for the newly diagnosed, and 8.8 +/- 4.0 per 10(6) cells for the patients with chronic disease) was not significantly different (p > 0.05) from that of the control group (6.8 +/- 6.4 per 10(6) cells). These data do not support the concept that patients with HT have an increased number of actively dividing T cells in the circulation compared to healthy controls. Autoreactive T cells may be activated mainly in situ or home readily to the thyroid in the early stages of the disease and reach a nonexpansion stage as the chronic disease is stabilized.
桥本甲状腺炎（HT）的一个显著特征是T细胞介导的甲状腺破坏，导致甲状腺功能减退。与其他自身免疫性疾病一样，HT的一个核心前提是自身反应性T细胞必须响应自身抗原进行分裂，在激活过程中积累随机的自发突变。在这里，我们通过使用编码补救途径酶次黄嘌呤-鸟嘌呤磷酸核糖转移酶的hprt基因作为体细胞突变的监测指标来检验这一假设。选择了11名新诊断的HT患者和10名慢性病患者进行研究，而10名健康个体作为对照。外周血T细胞在有限稀释条件下于6-硫鸟嘌呤存在下培养，并通过泊松统计计算存活的突变hprt(-) T细胞的频率（MF）。观察到两个患者组的平均MF值（新诊断患者为每10(6) 个细胞6.6 +/- 5.8，慢性病患者为每10(6) 个细胞8.8 +/- 4.0）与对照组（每10(6) 个细胞6.8 +/- 6.4）相比无显著差异（p > 0.05）。这些数据不支持与健康对照相比，HT患者循环中活跃分裂的T细胞数量增加的概念。自身反应性T细胞可能主要在原位被激活，或在疾病早期容易归巢到甲状腺，并在慢性病稳定时进入非扩增阶段。
