ABSTRACT

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 CD8⁺GITR⁺ T cells to more fully assess the T cell activation dysfunction in AA. We for the first time demonstrated significantly decreased percentage of CD8⁺GITR⁺ T cells in AA, and CD8⁺GITR⁺CTLA-4⁺ T cells were significantly higher in patients with AA compared with HIs. Conversely, the percentage of CD8⁺GITR⁺granzyme B⁺ and CD8⁺GITR⁺perforin⁺ T cells in AA patients was significantly reduced. Our preliminary data illustrate that the CD8⁺GITR⁺ T cell population might negatively regulate overactive T cell activation in AA.

摘要

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。过度活化的CD8 ⁺ T 细胞在 AA 的发病机制中起主导作用，这可能是由于 T 细胞中的共刺激和共抑制信号失衡所致。在这项研究中，我们首先研究了 OX40、4-1BB、GITR、ICOS、CTLA-4、LAG-3 和 TIM-3 在来自未经治疗的 AA 患者和健康个体 (HIs) 的CD8 ⁺ T 细胞上的表达。细胞术。此外，我们进一步分析了 CD8 ⁺ GITR ⁺ T 细胞的表型和功能特征，以更全面地评估 AA 中的 T 细胞活化功能障碍。我们首次证明 CD8 ⁺ GITR ^{+ 的}百分比显着降低AA 中的 T 细胞和 CD8 ⁺ GITR ⁺ CTLA-4 ⁺ T 细胞在 AA 患者中显着高于 HI。相反，AA患者CD8 ⁺ GITR ⁺颗粒酶B ⁺和CD8 ⁺ GITR ⁺穿孔素⁺ T细胞的百分比显着降低。我们的初步数据表明，CD8 ⁺ GITR ⁺ T 细胞群可能会对 AA 中过度活跃的 T 细胞活化产生负向调节。