Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China.
Department of Hematology, Guangzhou First People's Hospital, the Second Affiliated Hospital of South China University of Technology, Guangzhou, China.
Immunol Invest. 2021 May;50(4):406-415. doi: 10.1080/08820139.2020.1770785. Epub 2020 May 28.
Aplastic anemia (AA) is a T cell immune-mediated autoimmune disease. Overactivated CD8 T cells play a leading role in the pathogenesis of AA, which may be due to disbalance in costimulatory and coinhibitory signals in T cells. In this study, we firstly investigated the expression of OX40, 4-1BB, GITR, ICOS, CTLA-4, LAG-3, and TIM-3 on CD8 T cells from untreated patients with AA and healthy individuals (HIs) by flow cytometry. Moreover, we further analyzed the phenotype and functional characteristics of CD8GITR T cells to more fully assess the T cell activation dysfunction in AA. We for the first time demonstrated significantly decreased percentage of CD8GITR T cells in AA, and CD8GITRCTLA-4 T cells were significantly higher in patients with AA compared with HIs. Conversely, the percentage of CD8GITRgranzyme B and CD8GITRperforin T cells in AA patients was significantly reduced. Our preliminary data illustrate that the CD8GITR T cell population might negatively regulate overactive T cell activation in AA.
再生障碍性贫血(AA)是一种 T 细胞免疫介导的自身免疫性疾病。过度激活的 CD8 T 细胞在 AA 的发病机制中起主导作用,这可能是由于 T 细胞中共刺激和共抑制信号的失衡所致。在这项研究中,我们首先通过流式细胞术检测了未经治疗的 AA 患者和健康个体(HIs)中 CD8 T 细胞上 OX40、4-1BB、GITR、ICOS、CTLA-4、LAG-3 和 TIM-3 的表达。此外,我们进一步分析了 CD8GITR T 细胞的表型和功能特征,以更全面地评估 AA 中 T 细胞激活功能障碍。我们首次证明,AA 患者中 CD8GITR T 细胞的比例显著降低,与 HIs 相比,AA 患者的 CD8GITRCTLA-4 T 细胞明显升高。相反,AA 患者的 CD8GITRgranzyme B 和 CD8GITRperforin T 细胞的比例显著降低。我们的初步数据表明,CD8GITR T 细胞群可能负调节 AA 中过度活跃的 T 细胞激活。