Department of Pediatrics, University of Würzburg, Josef-Schneider-Str, 2, Würzburg, Germany.
BMC Endocr Disord. 2013 Sep 5;13:34. doi: 10.1186/1472-6823-13-34.
Alterations in the naive T cell subpopulations have been demonstrated in patients with T cell mediated autoimmune disorders, reminiscent of immunological changes found in the elderly during immunosenescence, including the switch from CD45RA + to CD45RO + T cells and decreased thymic function with increased compensatory proliferative mechanisms, partly associated with latent Cytomegalovirus (CMV) infection. The present study was aimed to investigate proportions of lymphocytes, their relation to CMV-seropositivity and the replicative history of CD45RA + expressing T cells in Hashimoto's thyroiditis (HT, n = 18) and healthy controls (HC, n = 70).
Proportions of peripheral T cells were investigated by flow cytometry. The replicative history was assessed by T cell receptor excision circles (TRECs) and relative telomere length (RTL). Expression of CD62L was analyzed by immunohistochemistry in thyroid sections. The role of CMV was assessed by serology, ELISPOT assay and in situ hybridization.
Our results demonstrated a significant increase of CD28-negative T cells, associated with CMV-seropositivity in HT patients. HT showed abundant CD45RO + T cells with peripheral loss of CD62L-expressing CD8 + CD45RA + T cells, the latter mainly depending on disease duration. CD62L was expressed in thyroid lymphocyte infiltrations. The diagnosis of HT and within the HT group CMV-seropositivity were the main determinants for the loss of CD28 expression. RTL was not different between HC and HT. HT showed significantly lower TRECs in CD4 + CD45RA + T cells compared to HC.
Patients with HT display a peripheral T cell phenotype reminiscent of findings in elderly persons or other autoimmune disorders. Whether these mechanisms are primary or secondary to the immunological alterations of autoimmune conditions should be investigated in longitudinal studies which may open research on new therapeutic regimes for treatment of HT and associated autoimmune diseases.
在 T 细胞介导的自身免疫性疾病患者中，已观察到幼稚 T 细胞亚群的改变，这让人联想到免疫衰老过程中老年人中发现的免疫变化，包括从 CD45RA+向 CD45RO+T 细胞的转变，以及胸腺功能下降和代偿性增殖机制增加，部分与潜伏性巨细胞病毒 (CMV) 感染有关。本研究旨在探讨桥本甲状腺炎 (HT，n=18) 和健康对照者 (HC，n=70) 外周血淋巴细胞比例及其与 CMV 血清阳性的关系，以及 CD45RA+表达 T 细胞的复制历史。
通过流式细胞术检测外周 T 细胞的比例。通过 T 细胞受体切除环 (TREC) 和相对端粒长度 (RTL) 评估复制历史。通过免疫组化分析甲状腺切片中 CD62L 的表达。通过血清学、ELISPOT 检测和原位杂交评估 CMV 的作用。
我们的结果表明，HT 患者 CD28 阴性 T 细胞显著增加，与 CMV 血清阳性有关。HT 显示大量的 CD45RO+T 细胞，外周 CD8+CD45RA+T 细胞丢失 CD62L 表达，后者主要取决于疾病持续时间。CD62L 在甲状腺淋巴细胞浸润中表达。HT 的诊断和 HT 组内 CMV 血清阳性是 CD28 表达缺失的主要决定因素。HC 和 HT 之间的 RTL 没有差异。与 HC 相比，HT 患者 CD4+CD45RA+T 细胞中的 TRECs 明显降低。
HT 患者表现出类似于老年人或其他自身免疫性疾病的外周 T 细胞表型。这些机制是自身免疫性疾病免疫改变的原发性还是继发性，应在纵向研究中进行探讨，这可能为 HT 及相关自身免疫性疾病的治疗开辟新的治疗方案研究。
