Zong Yan, Liu Yuanyuan, Wang Junyang, Rastegar-Kashkooli Yousef, Fu Peiji, Chen Shuai, Zhang Qianlin, Huang Maosen, Wang Junmin, Zhang Jiewen, Wang Jian, Jiang Chao
Department of Neurology, People's Hospital of Zhengzhou University & Henan Provincial People's Hospital, Zhengzhou, P. R. China.
Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, P. R. China.
J Neurochem. 2025 Feb;169(2):e16246. doi: 10.1111/jnc.16246. Epub 2024 Oct 22.
T lymphocytes play a vital role in the immune-inflammatory response following a stroke. However, the specific mechanisms behind the contrasting functions of T cells in the brain and peripheral tissues after a stroke remain unclear and require further investigation. T-cell receptors (TCRs) are essential in controlling how T lymphocytes develop and become active. This study aims to gain a deeper understanding of the biological function of T lymphocytes by analyzing the TCR repertoire in patients who have experienced an acute ischemic stroke (AIS). High-throughput TCR sequencing was conducted on peripheral blood samples from 25 AIS patients and 10 healthy controls. We compared the percentage of T cells and the characteristics of the TCR repertoire, specifically focusing on the recombination of V(D)J gene fragments and the diversity of the complementarity determining region 3 (CDR3) of the Vβ gene. Additionally, this study analyzed the potential biological significance of the skewed TCR repertoire in AIS patients. In patients with AIS, the proportion of circulating lymphocytes (LY%) decreased while the systemic immune-inflammatory index (SII) increased compared to healthy controls. The average number of TCR read pairs decreased, corresponding with the presence of lymphopenia. However, the recombination of V(D)J gene fragments, the number of CDR3 clonotypes, and the diversity of CDR3 was elevated in the peripheral blood of AIS patients. Furthermore, the increased number of CDR3 amino acid or nucleotide clonotypes was negatively correlated with neurologic deficits but positively correlated with AIS patients' systemic immune condition and functional outcomes. Our findings suggest that both immunosuppression and enhanced antigen-specific T-cell response may exist in the periphery of the AIS patients. Further investigation into the mechanisms underlying these opposing changes may lead to the discovery of novel targets to reverse immunosuppression or mitigate the detrimental effects of T cells in the lesioned brain of AIS patients.
T淋巴细胞在中风后的免疫炎症反应中起着至关重要的作用。然而,中风后T细胞在大脑和外周组织中功能相反的具体机制仍不清楚,需要进一步研究。T细胞受体(TCR)在控制T淋巴细胞的发育和激活方式方面至关重要。本研究旨在通过分析急性缺血性中风(AIS)患者的TCR库,更深入地了解T淋巴细胞的生物学功能。对25例AIS患者和10例健康对照者的外周血样本进行了高通量TCR测序。我们比较了T细胞的百分比和TCR库的特征,特别关注V(D)J基因片段的重组以及Vβ基因互补决定区3(CDR3)的多样性。此外,本研究分析了AIS患者中TCR库倾斜的潜在生物学意义。与健康对照相比,AIS患者循环淋巴细胞比例(LY%)下降,全身免疫炎症指数(SII)升高。TCR读取对的平均数减少,与淋巴细胞减少的存在相对应。然而,AIS患者外周血中V(D)J基因片段的重组、CDR3克隆型的数量和CDR3的多样性均升高。此外,CDR3氨基酸或核苷酸克隆型数量的增加与神经功能缺损呈负相关,但与AIS患者的全身免疫状况和功能结局呈正相关。我们的研究结果表明,AIS患者外周可能同时存在免疫抑制和增强的抗原特异性T细胞反应。对这些相反变化背后机制的进一步研究可能会发现新的靶点,以逆转免疫抑制或减轻T细胞对AIS患者受损大脑的有害影响。