Kudryavtsev Igor, Benevolenskaya Stanislava, Serebriakova Maria, Grigor'yeva Irina, Kuvardin Evgeniy, Rubinstein Artem, Golovkin Alexey, Kalinina Olga, Zaikova Ekaterina, Lapin Sergey, Maslyanskiy Alexey
Federal State Budgetary Institution "Almazov National Medical Research Centre" of the Ministry of Health of the Russian Federation, St. Petersburg 197341, Russia.
Federal State Budgetary Educational Institution of Higher Education Academician I.P. Pavlov First St. Petersburg State Medical University of the Ministry of Healthcare of Russian Federation, St. Petersburg 197022, Russia.
Biomedicines. 2023 Oct 13;11(10):2778. doi: 10.3390/biomedicines11102778.
Currently, multiple studies have indicated that CD8+ T lymphocytes play a role in causing damage to the exocrine glands through acinar injury in primary Sjögren's syndrome (pSS). The aim of this research was to assess the imbalance of circulating CD8+ T cell subsets. We analyzed blood samples from 34 pSS patients and 34 healthy individuals as controls. We used flow cytometry to enumerate CD8+ T cell maturation stages, using as markers CD62L, CD28, CD27, CD4, CD8, CD3, CD45RA and CD45. For immunophenotyping of 'polarized' CD8+ T cell subsets, we used the following monoclonal antibodies: CXCR5, CCR6, CXCR3 and CCR4. The findings revealed that both the relative and absolute numbers of 'naïve' CD8+ T cells were higher in pSS patients compared to the healthy volunteers. Conversely, the proportions of effector memory CD8+ T cells were notably lower. Furthermore, our data suggested that among patients with pSS, the levels of cytotoxic Tc1 CD8+ T cells were reduced, while the frequencies of regulatory cytokine-producing Tc2 and Tc17 CD8+ T cells were significantly elevated. Simultaneously, the Tc1 cell subsets displayed a negative correlation with immunoglobulin G, rheumatoid factor, the Schirmer test and unstimulated saliva flow. On the other hand, the Tc2 cell subsets exhibited a positive correlation with these parameters. In summary, our study indicated that immune dysfunction within CD8+ T cells, including alterations in Tc1 cells, plays a significant role in the development of pSS.
目前,多项研究表明,在原发性干燥综合征(pSS)中,CD8 + T淋巴细胞通过腺泡损伤对外分泌腺造成损害。本研究的目的是评估循环CD8 + T细胞亚群的失衡。我们分析了34例pSS患者和34例健康个体作为对照的血样。我们使用流式细胞术来计数CD8 + T细胞的成熟阶段,使用CD62L、CD28、CD27、CD4、CD8、CD3、CD45RA和CD45作为标志物。对于“极化”CD8 + T细胞亚群的免疫表型分析,我们使用了以下单克隆抗体:CXCR5、CCR6、CXCR3和CCR4。研究结果显示,与健康志愿者相比,pSS患者中“幼稚”CD8 + T细胞的相对数量和绝对数量均更高。相反,效应记忆CD8 + T细胞的比例明显更低。此外,我们的数据表明,在pSS患者中,细胞毒性Tc1 CD8 + T细胞水平降低,而产生调节性细胞因子的Tc2和Tc17 CD8 + T细胞频率显著升高。同时,Tc1细胞亚群与免疫球蛋白G、类风湿因子、Schirmer试验和非刺激性唾液流量呈负相关。另一方面,Tc2细胞亚群与这些参数呈正相关。总之,我们的研究表明,CD8 + T细胞内的免疫功能障碍,包括Tc1细胞的改变,在pSS的发病机制中起重要作用。