Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.
Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China.
J Leukoc Biol. 2020 Jan;107(1):57-67. doi: 10.1002/JLB.4A0818-313RR. Epub 2019 Aug 6.
Most information about the immune status of NK cells during sepsis has been obtained from animal models, athough data from clinical septic patients is limited. In this study, we aimed to decipher NK cell immunity of septic patients in a more comprehensive way. We found that cytotoxicity of NK cells dramatically decreased during sepsis, likely due to the reduction of cluster of differentiation (CD)3 CD56 NK cells and a shift of phenotypic changes of NK group 2 member (NKG2) receptors, natural cytotoxicity receptors (NCRs) and killer immunoglobulin-like receptors (KIRs) toward inhibitory receptors demonstrated by CD3 CD56 NK cells in septic patients. Expression of the activation indicator CD69 and cytotoxic associated marker CD107a on CD3 CD56 NK cells in healthy adults was significantly lower than that of septic patients. Although perforin and granzyme B on CD3 CD56 NK cells from all groups exhibited equivalently high levels, CD3 CD56 NK cells from septic patients exhibited a much lower fold increase of CD69 and CD107a compared with healthy adults after coculturing with K562 cells in vitro. Cytokine production of IFN-γ and TNF-α on CD3 CD56 NK cells in septic patients was also impaired after stimulation by PMA and ionomycin. We found that the proportion of NK cells in lymphocytes was negatively associated with patient 28 d death in septic patients. Phenotypic changes of a shift toward inhibitory receptors and impairment of effector functions of NK cells might be an important mechanism of immunosuppression during sepsis.
大多数关于脓毒症期间 NK 细胞免疫状态的信息都是从动物模型中获得的，尽管临床脓毒症患者的数据有限。在这项研究中，我们旨在更全面地解析脓毒症患者的 NK 细胞免疫。我们发现 NK 细胞的细胞毒性在脓毒症期间显著降低，可能是由于分化群 (CD)3 CD56 NK 细胞减少以及 NK 组 2 成员 (NKG2) 受体、自然细胞毒性受体 (NCR) 和杀伤免疫球蛋白样受体 (KIR) 的表型变化向 NK 细胞的抑制性受体转移。脓毒症患者 CD3 CD56 NK 细胞表现出的变化。健康成年人 CD3 CD56 NK 细胞上的激活标志物 CD69 和细胞毒性相关标志物 CD107a 的表达明显低于脓毒症患者。尽管来自所有组的 CD3 CD56 NK 细胞上的穿孔素和颗粒酶 B 表达水平相当高，但与健康成年人相比，来自脓毒症患者的 CD3 CD56 NK 细胞在与 K562 细胞体外共培养后，CD69 和 CD107a 的 fold increase 明显较低。脓毒症患者 CD3 CD56 NK 细胞经 PMA 和离子霉素刺激后 IFN-γ和 TNF-α 的细胞因子产生也受损。我们发现，脓毒症患者淋巴细胞中 NK 细胞的比例与患者 28 天死亡呈负相关。NK 细胞向抑制性受体表型变化和效应功能受损可能是脓毒症期间免疫抑制的一个重要机制。
