Department of Blood Transfusion, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Department of Laboratory Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China.
J Immunol Res. 2018 Dec 24;2018:8972572. doi: 10.1155/2018/8972572. eCollection 2018.
Follicular helper T (Tfh) cells are critical for high-affinity antibody generation and B cell maturation and differentiation, which play important roles in autoimmune diseases. Graves' disease (GD) is one prototype of common organ-specific autoimmune thyroid diseases (AITD) characterized by autoreactive antibodies, suggesting a possible role for Tfh cells in the pathogenesis of GD. Our objective was to explore the role of circulating Tfh cell subsets and associated plasma cells (PCs) in patients with GD.
Thirty-six patients with GD and 20 healthy controls (HC) were enrolled in this study. The frequencies of circulating Tfh cell subsets and PCs were determined by flow cytometry, and plasma cytokines, including interleukin- (IL-) 21, IL-4, IL-17A, and interferon- (IFN-) , were measured using an enzyme-linked immunosorbent assay (ELISA). The mRNA expression of transcription factors (Bcl-6, T-bet, GATA-3, and RORt) in peripheral blood mononuclear cells (PBMCs) was evaluated by real-time quantitative PCR. Compared with HC, the frequencies of circulating CD4CXCR5CD45RATfh (cTfh) cells with ICOS and PD-1 expression, the Tfh2 subset (CXCR3CCR6Tfh) cells, and PCs (CD19CD27CD38) were significantly increased in the GD patients, but the frequencies of Tfh1 (CXCR3CCR6Tfh) and Tfh17 (CXCR3CCR6Tfh) subset cells among CD4T cells were significantly decreased in GD patients. The plasma concentrations of IL-21, IL-4, and IL-17A were elevated in GD patients. Additionally, a positive correlation was found between the frequency of PD-1Tfh cells (Tfh2 or PCs) and plasma IL-21 concentration (or serum TPO-Ab levels). The mRNA levels of transcription factors (GATA-3 and RORt) were significantly increased, but T-bet and Bcl-6 mRNA expression was not obviously varied in PBMCs from GD patients. Interestingly, Tfh cell subsets and PCs from GD patients were partly normalized by treatment.
Circulating Tfh cell subsets and PCs might play an important role in the pathogenesis of GD, which are potential clues for GD patients' interventions.
滤泡辅助 T（Tfh）细胞对于高亲和力抗体的产生和 B 细胞的成熟和分化至关重要，这些过程在自身免疫性疾病中发挥重要作用。格雷夫斯病（GD）是一种常见的器官特异性自身免疫性甲状腺疾病（AITD）的原型，其特征是自身反应性抗体，这表明 Tfh 细胞可能在 GD 的发病机制中起作用。我们的目的是探讨循环 Tfh 细胞亚群及其相关浆细胞（PC）在 GD 患者中的作用。
本研究纳入 36 名 GD 患者和 20 名健康对照者（HC）。通过流式细胞术测定循环 Tfh 细胞亚群和 PC 的频率，并采用酶联免疫吸附试验（ELISA）测定包括白细胞介素（IL）-21、IL-4、IL-17A 和干扰素（IFN）-γ在内的血浆细胞因子水平。采用实时定量 PCR 评估外周血单个核细胞（PBMC）中转录因子（Bcl-6、T-bet、GATA-3 和 RORt）的 mRNA 表达。与 HC 相比，GD 患者外周血中表达 ICOS 和 PD-1 的循环 CD4+CXCR5+CD45RA+Tfh（cTfh）细胞、Tfh2 亚群（CXCR3+CCR6+Tfh）和 PC（CD19+CD27+CD38）的频率明显升高，而 CD4+T 细胞中 Tfh1（CXCR3+CCR6+Tfh）和 Tfh17（CXCR3+CCR6+Tfh）亚群细胞的频率明显降低。GD 患者的 IL-21、IL-4 和 IL-17A 血浆浓度升高。此外，PD-1+Tfh 细胞（Tfh2 或 PC）的频率与血浆 IL-21 浓度（或血清 TPO-Ab 水平）呈正相关。GD 患者 PBMC 中转录因子（GATA-3 和 RORt）的 mRNA 水平明显升高，但 T-bet 和 Bcl-6 mRNA 表达无明显变化。有趣的是，GD 患者的 Tfh 细胞亚群和 PC 经治疗后部分恢复正常。
循环 Tfh 细胞亚群和 PC 可能在 GD 的发病机制中起重要作用，这为 GD 患者的干预提供了潜在线索。
