Student Research Committee, Department of Immunology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
Golestan Rheumatology Research Center (GRRC), Golestan University of Medical Sciences, Gorgan, Iran.
Immunol Lett. 2020 Dec;228:76-82. doi: 10.1016/j.imlet.2020.10.005. Epub 2020 Oct 15.
Defect in T lymphocyte homeostasis could implicate initiation and development of rheumatoid arthritis (RA). Since PD-1 plays a key role in the regulation of T lymphocytes, its expression pattern in various CD8+ T cell subsets could be so effective in RA pathogenesis. Here, we investigated the expression of PD-1 and CXCR3 on CD8+CD28- T cells in association with the IFN-γ levels in patients with RA. A total of 42 RA patients, including 10 newly-diagnosed (ND) and 32 relapsed (RL) cases and also 20 healthy donors were enrolled. Phenotypic characterization of CD8+ T cells derived from peripheral blood (PB) and synovial fluid (SF) was performed by flow cytometry. The plasma and SF IFN-γ levels were also assessed by ELISA. The frequency of CD8+CD28- T cells showed no significant differences between patients and controls while its higher levels were observed in PB, versus SF of RL patients. Relapsed patients also showed higher CXCR3 and especially PD-1 expression on their CD8+CD28- T cells. The IFN-γ concentration was elevated in SF of ND patients while its plasma level was significantly lower in RL subgroup than controls. Although PD-1 could induce immune suppression in effector T cells, it is upregulated during inflammation and its overexpression on CD8+CD28- T cells within inflammatory synovium is associated with severity of disease in our cohort of RA patients.
T 淋巴细胞稳态缺陷可能与类风湿关节炎(RA)的发生和发展有关。由于 PD-1 在 T 淋巴细胞的调节中起着关键作用,其在各种 CD8+T 细胞亚群中的表达模式在 RA 发病机制中可能非常有效。在这里,我们研究了 PD-1 和 CXCR3 在 CD8+CD28-T 细胞上的表达与 RA 患者 IFN-γ 水平的关系。共纳入 42 例 RA 患者,包括 10 例初诊(ND)和 32 例复发(RL)患者,以及 20 例健康对照者。通过流式细胞术对来自外周血(PB)和滑液(SF)的 CD8+T 细胞进行表型特征分析。通过 ELISA 评估血浆和 SF IFN-γ 水平。CD8+CD28-T 细胞的频率在患者和对照组之间无显著差异,但其在 RL 患者的 PB 中,而非 SF 中水平较高。RL 患者的 CD8+CD28-T 细胞也表现出更高的 CXCR3 和 PD-1 表达,尤其是 PD-1。ND 患者的 SF 中 IFN-γ 浓度升高,而 RL 亚组的血浆水平明显低于对照组。尽管 PD-1 可在效应 T 细胞中诱导免疫抑制,但在炎症过程中其表达上调,其在炎症滑膜中 CD8+CD28-T 细胞上的过度表达与我们这组 RA 患者的疾病严重程度相关。