Analysis of T cell receptor Vβ diversity in peripheral CD4+ and CD8+ T lymphocytes in patients with autoimmune thyroid diseases
Analysis of T cell receptor Vβ diversity in peripheral CD4+ and CD8+ T lymphocytes in patients with autoimmune thyroid diseases
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DOI：
10.1111/j.1365-2249.2008.03842.x
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发表时间：
2009-02-01
影响因子：
4.6
通讯作者：
Yachie, A.
中科院分区：
文献类型：
--
作者：
Okajima, M.;Wada, T.;Yachie, A.
自身免疫性甲状腺疾病的特点是甲状腺内有对自身甲状腺抗原反应的CD4(+)和CD8(+)T淋巴细胞。早期分析T细胞受体(TCR)Vα基因用途的研究表明，甲状腺内的T淋巴细胞可以寡克隆扩增，但外周血T细胞却不能。然而，这些患者外周血中分离的CD4(+)和CD8(+)T细胞亚群的TCR Vβ多样性尚未完全确定。我们对13例Graves病和17例桥本甲状腺炎患者外周血中的CD8(+)和CD8(+)T细胞进行了互补决定区3(CDR3)分型和流式细胞术分析。流式细胞术证实两种疾病均有多克隆TCRVβ谱系。相反，CDR3分型显示桥本甲状腺炎患者外周CD8(+)T细胞的TCR Vβ偏斜率显著高于健康成人，而CD4(+)T细胞的TCR Vβ偏斜率则不明显。我们发现，在那些患病时间超过5年并需要甲状腺激素替代的患者中，CDR3的大小分布有更不对称的趋势。Graves病患者的CD4(+)和CD8(+)T细胞均无偏斜现象。这些结果表明，桥本甲状腺炎患者外周血中可检测到CD8(+)T细胞的克隆性增殖，并可能支持CD8(+)T细胞在桥本甲状腺炎甲状腺细胞介导的自身免疫攻击中的作用。
Autoimmune thyroid diseases are characterized by intrathyroidal infiltration of CD4(+) and CD8(+) T lymphocytes reactive to self-thyroid antigens. Early studies analysing T cell receptor (TCR) V alpha gene usage have shown oligoclonal expansion of intrathyroidal T lymphocytes but not peripheral blood T cells. However, TCR V beta diversity of the isolated CD4(+) and CD8(+) T cell compartments in the peripheral blood has not been characterized fully in these patients. We performed complementarity-determining region 3 (CDR3) spectratyping as well as flow cytometric analysis for the TCR V beta repertoire in peripheral CD4(+) and CD8(+) T cells from 13 patients with Graves' disease and 17 patients with Hashimoto's thyroiditis. Polyclonal TCR V beta repertoire was demonstrated by flow cytometry in both diseases. In contrast, CDR3 spectratyping showed significantly higher skewing of TCR V beta in peripheral CD8(+) T cells but not CD4(+) T cells among patients with Hashimoto's thyroiditis compared with healthy adults. We found trends towards a more skewed CDR3 size distribution in those patients having disease longer than 5 years and requiring thyroid hormone replacement. Patients with Graves' disease exhibited no skewing both in CD4(+) and CD8(+) T cells. These findings indicate that clonal expansion of CD8(+) T cells in Hashimoto's thyroiditis can be detected in peripheral blood and may support the role of CD8(+) T cells in cell-mediated autoimmune attacks on the thyroid gland in Hashimoto's thyroiditis.