Department of Pediatrics, Erciyes University School of Medicine, Kayseri, Turkey; Department of Pediatric Cardiology, Erciyes University School of Medicine, Kayseri, Turkey.
Department of Pediatric Cardiology, Erciyes University School of Medicine, Kayseri, Turkey.
Int J Cardiol. 2021 Jun 15;333:174-183. doi: 10.1016/j.ijcard.2021.02.020. Epub 2021 Feb 22.
Acute rheumatic fever (ARF) is an autoimmune disease caused by group A β-hemolytic streptococci (GAS) and may develop into rheumatic heart disease (RHD). The pathogenesis of ARF and RHD involves molecular mimicry and antibody-mediated mechanisms. T cell involvement is described in various stages of the disease. Mucosal associated invariant T (MAIT) cells are enriched at the mucosa and are present in the blood and may be activated by GAS.
In this study, we investigated the quantity and activity of CD3TCRVα7.2CD161 cells in the active and recovered ARF patients and healthy controls. Twenty newly diagnosed, 20 recovered-ARF children, and 20 healthy controls were enrolled in the study. Peripheral blood (PB) mononuclear cells were isolated by Ficoll-Paque density gradient. CD4, CD4 subsets of CD3CD161TCRVα7.2 cells and IFN-γ and TNF-α production were quantified by Flow cytometry.
Acute and recovered ARF patients had significantly elevated the number of CD3TCRVα7.2CD161 cells in their PB. Both CD4 and CD4 subsets were increased. Moreover, total CD3TCRVα7.2CD161 cell numbers were significantly higher in the recovered patients' PB compared with active ARF patients. In addition, CD3TCRVα7.2CD161 cells in both acute and recovered patients produced significantly more IFN-γ and TNF-α. Non-MAIT total CD3 T cell, CD4 and CD4 T cell subsets were also increased in active and recovered ARF patients and they also produced more IFN-γ and TNF-α.
Our data reveal that CD3TCRVα7.2CD161 cells are elevated and actively producing IFN-γ and TNF-α in acute and recovered ARF patients and may contribute to ARF pathology.
急性风湿热（ARF）是由 A 组β溶血性链球菌（GAS）引起的自身免疫性疾病，可能发展为风湿性心脏病（RHD）。ARF 和 RHD 的发病机制涉及分子模拟和抗体介导的机制。T 细胞参与了疾病的各个阶段。黏膜相关不变 T（MAIT）细胞在黏膜中丰富，并存在于血液中，可能被 GAS 激活。
在这项研究中，我们研究了活跃期和恢复期 ARF 患者及健康对照者中 CD3TCRVα7.2CD161 细胞的数量和活性。纳入 20 例新诊断的、20 例恢复期 ARF 患儿和 20 例健康对照者。采用 Ficoll-Paque 密度梯度离心法分离外周血（PB）单个核细胞。通过流式细胞术定量 CD4、CD3CD161TCRVα7.2 细胞的 CD4 亚群和 IFN-γ、TNF-α的产生。
急性和恢复期 ARF 患者 PB 中 CD3TCRVα7.2CD161 细胞数量明显升高。CD4 和 CD4 亚群均增加。此外，恢复期患者 PB 中总 CD3TCRVα7.2CD161 细胞数明显高于活跃期 ARF 患者。此外，急性和恢复期患者的 CD3TCRVα7.2CD161 细胞产生的 IFN-γ 和 TNF-α明显增多。活跃期和恢复期 ARF 患者的非 MAIT 总 CD3 T 细胞、CD4 和 CD4 T 细胞亚群也增加，并且它们也产生更多的 IFN-γ 和 TNF-α。
我们的数据表明，CD3TCRVα7.2CD161 细胞在急性和恢复期 ARF 患者中升高并积极产生 IFN-γ 和 TNF-α，可能有助于 ARF 发病机制。
