Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

背景：据报道，髓样来源的抑制细胞（MDSCs）在脓毒症期间持续升高。进行当前的研究以研究MDSC及其子集与潜在机制的免疫抑制作用。

方法：脾细胞的凋亡，T细胞的数量和PD-1的表达都表明了其免疫抑制状态。随时间确定MDSC及其子集的数量和PD-L1水平的动态。将具有高PD-L1水平的MDSC的子集与T细胞共培养，以观察其抑制作用。

结果：脓毒症后7天观察到腹部脓肿。CLP组中与器官功能相关的五个生物标志物均显着较高。存活率与脓毒症模型的中级严重程度一致。败血症期间脾细胞凋亡随时间增加；从败血症后的第一天开始，CD4 + T细胞减少；在第7天，CD8 + T细胞显着减少。从脓毒症的早期开始，脾脏中的PD-1表达上调，并且与T细胞的数量呈负相关。脓毒症后第1天的MDSCs较低，但后来增加到高水平。PMN-MDSC的动态类似于MDSC。MDSCs上的PD-L1在败血症后第1天最高；PMN-MDSC是表达PD-L1的主要子集。

结论： 脓毒症诱导的免疫抑制从很早就开始，PD-L1在MDSCs和主要子集PMN-MDSC上的高表达水平可能通过PD-L1 / PD-1轴对T细胞起关键的抑制作用。