Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcalá de Henares, Spain.
Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain.
Int J Mol Sci. 2023 Apr 11;24(8):7048. doi: 10.3390/ijms24087048.
Spinal cord injury (SCI) is a disabling neurological condition coursing with serious multisystem affections and morbidities. Changes in immune cell compartments have been consistently reported in previous works, representing a critical point of study for understanding the pathophysiology and progression of SCI from acute to chronic stages. Some relevant variations in circulating T cells have been noticed in patients with chronic SCI, although the number, distribution, and function of these populations remain to be fully elucidated. Likewise, the characterization of specific T cell subpopulations and their related cytokine production can aid in understanding the immunopathological role of T cells in SCI progression. In this sense, the objective of the present study was to analyze and quantify the total number of different cytokine-producers T cells in the serum of patients with chronic SCI ( = 105) in comparison to healthy controls ( = 38) by polychromatic flow cytometry. Having this goal, we studied CD4 and CD8 lymphocytes as well as naïve, effector, and effector/central memory subpopulations. SCI patients were classified according to the duration of the lesion in chronic SCI with a short period of evolution (SCI-SP) (comprised between 1 and 5 years since initial injury), early chronic phase (SCI-ECP) (between 5 and 15 years since initial injury) and late-chronic phase (SCI-LCP) (>15 years since initial injury). Our results show that patients with chronic SCI exhibited an altered immune profile of cytokine-producer T cells, including CD4/CD8 naïve, effector, and memory subpopulations in comparison to HC. In particular, IL-10 and IL-9 production seems to be importantly altered, especially in patients with SCI-LCP, whereas changes in IL-17, TNF-α, and IFN-γ T cell populations have also been reported in this and other chronic SCI groups. In conclusion, our study demonstrates an altered profile of cytokine-producer T cells in patients with chronic SCI, with marked changes throughout the course of the disease. In more detail, we have observed significant variations in cytokine production by circulating naive, effector, and effector/central memory CD4 and CD8 T cells. Future studies should be directed to explore the possible clinical consequences of these changes or develop additional translational approaches in these groups of patients.
脊髓损伤 (SCI) 是一种致残性的神经系统疾病,伴有严重的多系统损伤和疾病。在之前的研究中,一致报道了免疫细胞区室的变化,这代表了理解 SCI 从急性到慢性阶段的病理生理学和进展的一个关键研究点。在慢性 SCI 患者中已经注意到循环 T 细胞的一些相关变化,尽管这些细胞的数量、分布和功能仍有待充分阐明。同样,特定 T 细胞亚群的特征及其相关细胞因子的产生可以帮助理解 T 细胞在 SCI 进展中的免疫病理作用。在这方面,本研究的目的是通过多色流式细胞术分析和量化慢性 SCI 患者(n=105)与健康对照组(n=38)血清中不同细胞因子产生 T 细胞的总数。为了实现这一目标,我们研究了 CD4 和 CD8 淋巴细胞以及幼稚、效应和效应/中央记忆亚群。根据慢性 SCI 病变的持续时间,将 SCI 患者分为短病程组(SCI-SP)(从最初损伤开始 1-5 年)、早期慢性期组(SCI-ECP)(从最初损伤开始 5-15 年)和晚期慢性期组(SCI-LCP)(从最初损伤开始>15 年)。我们的结果表明,与 HC 相比,慢性 SCI 患者表现出细胞因子产生 T 细胞的免疫谱改变,包括 CD4/CD8 幼稚、效应和记忆亚群。特别是,IL-10 和 IL-9 的产生似乎受到了重要影响,尤其是在 SCI-LCP 患者中,而在其他慢性 SCI 组中也报道了 IL-17、TNF-α 和 IFN-γ T 细胞群的变化。总之,我们的研究表明,慢性 SCI 患者存在细胞因子产生 T 细胞的改变谱,随着疾病的发展而发生明显变化。更详细地说,我们观察到循环 CD4 和 CD8 幼稚、效应和效应/中央记忆 T 细胞中细胞因子产生的显著变化。未来的研究应致力于探索这些变化的可能临床后果,或在这些患者群体中开发额外的转化方法。