Analysis of regulatory T lymphocytes in patients with traumatic brain injury

Anna O. Norka, S. V. Vorobyev, R. N. Kuznetsova, M. K. Serebriakova, I V. Kudryavtsev, S. N. Kovalenko, D. N. Monashenko
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Abstract

In recent years, traumatic brain injury (TBI) has been one of the most urgent medical and social problems due to its prevalence, predominantly affecting young people of working age, causing high mortality, disability and economic costs for treatment and subsequent rehabilitation of patients. At present, the role of patients immune system in evolving neuroinflammation after traumatic brain injury has been proven. Treg cell populations represent an important factor determining the outcome of the disease due to promoting induction of immunological tolerance, being a significant component of immunoregulation. As a result of our study, we found a decrease in the relative content of Treg within the total lymphocyte pool of peripheral blood, which has the CD3+CD4+CD25bright phenotype in patients of the 3rd and 4th groups, in comparison with the data from control group. Moreover, a decreased relative content of Tregs (CD4+CD25+T cells) was revealed which is due to the degree of brain tissue damage and, as a result, their migration to suppress inflammation due to production of anti-inflammatory cytokines (TGF-, IL-10). The Treg population is heterogeneous, thus prompting us for analysis of the Treg subpopulations profile based on the expression of CD45R0 and CD62L. When assessing subpopulations of regulatory T lymphocytes within CD45Ro and CD62L, significant changes were found only in patients with brain contusion. The changes were revealed within the pool of naive T regulatory lymphocytes with the CD3+CD4+CD25brightCD39+ Treg phenotype, capable of producing a wide range of cytokines specific for Th1, Th2, Th17, in patients with mild, moderate and severe TBI. Meanwhile, the level of highly active CD3+CD4+CD25brightCD73+ Tregs was significantly reduced in patients with moderate and severe TBI. These changes indicate an imbalance in immunoregulatory processes resulting from extensive damage to brain tissues.
外伤性脑损伤患者调节性T淋巴细胞的分析
近年来,创伤性脑损伤(TBI)因其普遍性而成为最紧迫的医疗和社会问题之一,主要影响到工作年龄的年轻人,造成高死亡率、残疾和患者治疗和随后康复的经济成本。目前,患者免疫系统在创伤性脑损伤后神经炎症发展中的作用已经得到证实。Treg细胞群是决定疾病结局的重要因素,因为它促进了免疫耐受的诱导,是免疫调节的重要组成部分。我们的研究发现,与对照组相比,第3组和第4组患者外周血中CD3+CD4+CD25bright表型的总淋巴细胞池中Treg的相对含量有所下降。此外,我们还发现Tregs (CD4+CD25+T细胞)的相对含量降低,这是由于脑组织损伤程度所致,因此它们通过产生抗炎细胞因子(TGF-, IL-10)而迁移到抑制炎症。Treg群体是异质的,因此促使我们基于CD45R0和CD62L的表达分析Treg亚群体的概况。当评估CD45Ro和CD62L内调节性T淋巴细胞亚群时,仅在脑挫伤患者中发现显著变化。在轻度、中度和重度TBI患者中,CD3+CD4+CD25brightCD39+ Treg表型的幼稚T调节性淋巴细胞池中发现了这些变化,这些淋巴细胞能够产生广泛的Th1、Th2、Th17特异性细胞因子。同时,中重度TBI患者的高活性CD3+CD4+CD25brightCD73+ Tregs水平显著降低。这些变化表明免疫调节过程的不平衡是由脑组织的广泛损伤引起的。
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