Department of Clinical Immunology, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, Poland.
Laboratory of Cellular and Genetic Therapies, Center for Preclinical Research, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland.
Int J Mol Sci. 2024 Oct 28;25(21):11576. doi: 10.3390/ijms252111576.
polysaccharides are natural immunomodulators. SeLe30, analyzed in this study, is a new mixture of selenium-enriched linear 1,4-α-glucans and 1,3-β- and 1,6-β-glucans isolated from L. edodes mycelium. In the present study, we evaluated its immunomodulatory properties in human T cells. Peripheral blood mononuclear cells (PBMCs) and T cells were isolated from healthy donors' buffy coats. The effects of SeLe30 on CD25, CD366, and CD279 expression, the subsets of CD8+ T cells, and IFN-γ, IL-6, and TNF-α production were analyzed. SeLe30 downregulated CD25, CD279, and CD366 expression on T cells stimulated by the anti-CD3 antibody (Ab) and upregulated in unstimulated and anti-CD3/CD28-Abs-stimulated T cells. It increased the percentage of central memory CD8+ T cells in unstimulated PBMCs and naïve and central memory T cells in anti-CD3-Ab-stimulated PBMCs. SeLe30 decreased the number of central memory and naïve CD8+ T cells in anti-CD3/CD28-stimulated T cells, whereas, in PBMCs, it reduced the percentage of effector memory CD8+ T cells. Moreover, SeLe30 upregulated cytokine production. SeLe30 exhibits context-dependent effects on T cells. It acts on unstimulated T cells, affecting their activation while increasing the expression of immune checkpoints, which sensitizes them to inhibitory signals that can silence this activation. In the case of a lack of costimulation, SeLe30 exhibits an inhibitory effect, reducing T-cell activation. In cells stimulated by dual signals, its effect is further enhanced, again increasing the "safety brake" of CD366 and CD279. However, the final SeLe30 effect is mediated by its indirect impacts by altering interactions with other immune cells.
多糖是天然的免疫调节剂。本研究中分析的 SeLe30 是一种从香菇菌丝体中分离出的新型富硒线性 1,4-α-葡聚糖与 1,3-β-和 1,6-β-葡聚糖的混合物。在本研究中，我们评估了其在人类 T 细胞中的免疫调节特性。外周血单核细胞（PBMCs）和 T 细胞从健康供体的白细胞层中分离出来。分析了 SeLe30 对 CD25、CD366 和 CD279 表达、CD8+T 细胞亚群以及 IFN-γ、IL-6 和 TNF-α产生的影响。SeLe30 下调了由抗 CD3 抗体（Ab）刺激的 T 细胞上的 CD25、CD279 和 CD366 的表达，并上调了未刺激和抗 CD3/CD28-Abs 刺激的 T 细胞上的表达。它增加了未刺激 PBMCs 中中央记忆 CD8+T 细胞和抗 CD3-Ab 刺激 PBMCs 中幼稚和中央记忆 T 细胞的百分比。SeLe30 减少了抗 CD3/CD28 刺激的 T 细胞中中央记忆和幼稚 CD8+T 细胞的数量，而在 PBMCs 中，它降低了效应记忆 CD8+T 细胞的百分比。此外，SeLe30 上调了细胞因子的产生。SeLe30 对 T 细胞表现出依赖于上下文的作用。它作用于未受刺激的 T 细胞，影响其激活，同时增加免疫检查点的表达，使其对抑制信号敏感，从而可以沉默这种激活。在缺乏共刺激的情况下，SeLe30 表现出抑制作用，减少 T 细胞的激活。在双信号刺激的细胞中，其作用进一步增强，再次增加 CD366 和 CD279 的“安全刹车”。然而，SeLe30 的最终作用是通过其对其他免疫细胞相互作用的间接影响来介导的。
