Department of Emergency Medicine, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
Department of Geriatrics, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
Front Immunol. 2020 Jul 3;11:1299. doi: 10.3389/fimmu.2020.01299. eCollection 2020.
Myeloid derived suppressor cells (MDSCs) have been reported to keep elevating during sepsis. The current study was performed to investigate the immunosuppressive effect of MDSCs and their subsets with the underlying mechanisms. The immunosuppressive status was manifested by the apoptosis of splenocytes, quantity of T cells and PD-1 expression. The dynamics of quantity and PD-L1 level of MDSCs and the subsets were determined over time. The subset of MDSCs with high PD-L1 level was co-cultured with T cells to observe the suppressive effect. Abdominal abscess was observed after 7 days post-sepsis. Five biomarkers related to organ functions were all significantly higher in the CLP group. The survival rate was consistent with the middle grade severity of sepsis model. Apoptosis of splenocytes increased over time during sepsis; CD4 + T cell decreased from day 1 post-sepsis; CD8+ T cells significantly reduced at day 7. The PD-1 expression in spleen was upregulated from an early stage of sepsis, and negatively related with the quantity of T cells. MDSCs were low at day 1 post-sepsis, but increased to a high level later; the dynamics of PMN-MDSC was similar to MDSCs. PD-L1 on MDSCs was highest at day 1 post-sepsis; PMN-MDSC was the main subset expressing PD-L1. The PMN-MDSC with high PD-L1 expression level extracted on day 1 after surgery from CLP mice significantly inhibited the proliferation of T cells. Sepsis-induced immunosuppression is initiated from a very early stage, a high expression level of PD-L1 on MDSCs and the main subset, PMN-MDSC might play a critical role suppressive role on T cells through PD-L1/PD-1 axis.
髓系来源的抑制细胞（MDSCs）在脓毒症中一直被报道呈升高趋势。本研究旨在探讨 MDSCs 及其亚群的免疫抑制作用及其潜在机制。免疫抑制状态表现为脾细胞凋亡、T 细胞数量和 PD-1 表达减少。随着时间的推移，MDSCs 和其亚群的数量和 PD-L1 水平的动态变化被确定。具有高 PD-L1 水平的 MDSC 亚群与 T 细胞共培养，观察其抑制作用。脓毒症 7 天后观察到腹部脓肿。CLP 组的 5 种与器官功能相关的生物标志物均显著升高。存活率与中重度脓毒症模型一致。脓毒症过程中脾细胞凋亡随时间增加；CD4+T 细胞从脓毒症后第 1 天开始减少；CD8+T 细胞在第 7 天显著减少。脾 PD-1 表达在脓毒症早期上调，并与 T 细胞数量呈负相关。MDSCs 在脓毒症后第 1 天数量较低，但随后增加到高水平；PMN-MDSC 的动态变化与 MDSCs 相似。MDSCs 上的 PD-L1 在脓毒症后第 1 天表达最高；PMN-MDSC 是表达 PD-L1 的主要亚群。从 CLP 小鼠手术后第 1 天提取的高表达 PD-L1 的 PMN-MDSC 显著抑制了 T 细胞的增殖。脓毒症诱导的免疫抑制是从一个非常早期的阶段开始的，MDSCs 上高表达的 PD-L1 和主要亚群 PMN-MDSC 通过 PD-L1/PD-1 轴可能对 T 细胞发挥关键的抑制作用。
