Laboratory of Parasitology, General Karol Kaczkowski Military Institute of Hygiene and Epidemiology, 01-163 Warsaw, Poland.
Department of Parasitology, Institute of Functional Biology and Ecology, Faculty of Biology, University of Warsaw, 00-096 Warsaw, Poland.
Int J Mol Sci. 2022 Mar 16;23(6):3185. doi: 10.3390/ijms23063185.
Altered regulatory T cell (Treg) function could contribute to MS. The expression of activating and inhibitory receptors influences the activity of Tregs. Our aim was to investigate T cell phenotypes in relapsing-remitting MS (RRMS) patients at an early phase of the disease. We examined the influence of demographic parameters on the distribution of CD4+ and CD8+ T cell subclasses by generalized linear modeling. We also studied the expression of the following markers-CTLA-4, GITR, PD-1, FoxP3, Helios, CD28, CD62L, CD103-on T cell subsets from peripheral blood with a 14-color flow cytometry panel. We used an antibody array to define the profiles of 34 Th1/Th2/Th17 cytokines in the serum. Expression of PD-1 and GITR on CD4+ and CD8+ Tregs was decreased in RRMS patients. The proinflammatory factors IFN-, IL-17, IL-17F, TGF-1, TGF-3, IL-1SRII, IL-12 p40, sgp130, IL-6sR were significantly increased in RRMS patients. Therefore, a deficiency of PD-1 and GITR immune checkpoints on CD4+ and CD8+ Tregs is a feature of RRMS and might underlie impaired T cell control.
调节性 T 细胞（Treg）功能的改变可能导致多发性硬化症（MS）。激活和抑制性受体的表达影响 Treg 的活性。我们的目的是在 RRMS 患者疾病的早期阶段研究 T 细胞表型。我们通过广义线性建模检查了人口统计学参数对 CD4+和 CD8+T 细胞亚群分布的影响。我们还使用 14 色流式细胞术面板研究了外周血 T 细胞亚群中 CTLA-4、GITR、PD-1、FoxP3、Helios、CD28、CD62L 和 CD103 等标记物的表达。我们使用抗体阵列来定义血清中 34 种 Th1/Th2/Th17 细胞因子的图谱。RRMS 患者 CD4+和 CD8+Treg 上的 PD-1 和 GITR 表达降低。促炎因子 IFN-、IL-17、IL-17F、TGF-1、TGF-3、IL-1SRII、IL-12 p40、sgp130、IL-6sR 在 RRMS 患者中显著增加。因此，CD4+和 CD8+Treg 上 PD-1 和 GITR 免疫检查点的缺乏是 RRMS 的一个特征，可能是 T 细胞控制受损的基础。
