Department of Immunology, Center of Immunomolecular Engineering, Innovation & Practice Base for Graduate Students Education, Zunyi Medical University, Zunyi, China.
Department of Cardiology, Kunming Children's Hospital, Kunming, China.
Front Immunol. 2024 Oct 3;15:1457687. doi: 10.3389/fimmu.2024.1457687. eCollection 2024.
Kawasaki disease (KD), a common cause of acquired heart disease in children in developed countries, is primarily treated with intravenous immunoglobulin (IVIG), but some children demonstrate IVIG resistance with increased coronary artery injury risk. T cells have been demonstrated to be involved in the pathogenesis of KD and its treatment with IVIG. However, the role and mechanism of dual TCR T lymphocytes in the occurrence of KD and IVIG therapy remain unclear.
This study, based on scRNA-seq combined with TCR-seq technology, clustered the peripheral blood mononuclear cells of 3 healthy controls and 6 KD patients before and after IVIG treatment. Comparative analysis was conducted to investigate the differences in the proportion of single/dual receptor T cells, the characteristics of CDR3 repertoires, cell types, and the expression of transcription factors among the three groups. The study aimed to explore the correlation between dual TCR T cells and KD as well as IVIG treatment.
In our experimental results, we observed the presence of dual TCR T cells in all three groups. However, compared to the healthy control group and the IVIG-treated group, the KD patients before IVIG treatment exhibited a lower proportion of dual TCR T cells, with variability between samples, ranging from 4% to 15%. Notably, after IVIG treatment, the proportion of dual TCR T cells significantly increased, stabilizing above 12%, and these T cells also exhibited clonal expansion and a preference for V gene usage. In addition we found differences in dual TCR T cell subsets among the three groups, for example, IVIG treatment increases the proportion of dual TCR Treg cells, but it still remains below that of healthy control groups, significantly higher proportions of both dual TCR CD8 central and effector memory T cells in IVIG-treated KD patients, and differences in the expression of transcription factors between single and dual TCR T cells. These results suggest dual TCR T cells correlate with KD and IVIG treatment.
Dual TCR T lymphocytes, especially dual TCR CD8 T cells and Treg cells, play crucial roles in the pathogenesis of KD and during IVIG treatment, providing strong support for further elucidating KD pathogenesis and optimizing treatment strategies.
川崎病（KD）是发达国家儿童获得性心脏病的常见病因，主要采用静脉注射免疫球蛋白（IVIG）治疗，但部分患儿存在 IVIG 抵抗，增加冠状动脉损伤风险。T 细胞已被证实参与 KD 的发病机制及其 IVIG 治疗。然而，双 TCR T 淋巴细胞在 KD 发病机制及 IVIG 治疗中的作用和机制尚不清楚。
本研究基于 scRNA-seq 联合 TCR-seq 技术，对 3 例健康对照者和 6 例 KD 患者 IVIG 治疗前后的外周血单个核细胞进行聚类。通过比较分析，探讨三组间单/双受体 T 细胞比例、CDR3 库特征、细胞类型及转录因子表达的差异，探索双 TCR T 细胞与 KD 及 IVIG 治疗的相关性。
在本实验结果中，我们观察到所有三组均存在双 TCR T 细胞。然而，与健康对照组和 IVIG 治疗组相比，IVIG 治疗前 KD 患者的双 TCR T 细胞比例较低，且样本间存在变异性，范围为 4%至 15%。值得注意的是，IVIG 治疗后，双 TCR T 细胞比例显著增加，稳定在 12%以上，且这些 T 细胞还表现出克隆扩增和 V 基因使用偏好。此外，我们还发现三组间双 TCR T 细胞亚群存在差异，例如，IVIG 治疗增加了双 TCR Treg 细胞的比例，但仍低于健康对照组，IVIG 治疗的 KD 患者中双 TCR CD8 中央和效应记忆 T 细胞的比例显著更高，以及单和双 TCR T 细胞之间转录因子的表达存在差异。这些结果表明双 TCR T 细胞与 KD 和 IVIG 治疗相关。
双 TCR T 淋巴细胞，特别是双 TCR CD8 T 细胞和 Treg 细胞，在 KD 的发病机制和 IVIG 治疗中发挥重要作用，为进一步阐明 KD 的发病机制和优化治疗策略提供了有力支持。
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