Gao Dong-Na, Yang Zhi-Xiang, Qi Qing-Hui
Emergency Intensive Care Unit, The First Affiliated Hospital of Dalian Medical University, Dalian Medical University Dalian 116011, P. R. China.
Abdominal Second Division of Emergency, First Affiliated Hospital of Dalian Medical University Dalian 116011, P. R. China.
Int J Clin Exp Med. 2015 Oct 15;8(10):18998-9005. eCollection 2015.
This study aims to elucidate the roles of PD-1, Tim-3 and CTLA-4 in sepsis.
Sepsis patients (n = 182) were selected as sepsis group and divided into three subgroups: mild sepsis group, severe sepsis group and septic shock group; 185 healthy volunteers were enrolled as control group. Flow cytometry and blood routine examination were performed for T lymphocytes and surface co-stimulatory molecules expressions. Pearson correlation test was applied for the correlation of co-stimulatory molecules expressions on T lymphocytes with critical illness in sepsis. Logistic regression analysis was conducted for risk factors in sepsis.
Heart rate and WBC in subgroups were higher than control group (P < 0.05). The differences in APACHE II, SAP II and SOFA score among subgroups were statistically significant (P < 0.05). Compared with control group, lymphocyte ratio and percentage of CD4(+) T cells reduced in subgroups (P < 0.05). The differences in expression levels of CD4(+)PD-1(+), CD8(+)PD-1(+), and CD8(+)CTLA-4(+) showed statistical significances (P < 0.05). Apparently, expression levels of CD4(+)TIM-3(+), CD8(+)TIM-3(+), CD4(+)PD-1(+), CD8(+)PD-1(+), and CD4(+)CTLA-4(+) were positively correlated with APACHE II score (all P < 0.05). Logistic regression analysis showed that heart rate and expression level of CD4(+)PD-1(+) might be risk factors while the percentage of CD4(+) T cells might be a protective factor for sepsis (P < 0.05).
PD-1 aggravates immune responses consistent with promotion of T cell exhaustion in sepsis. Expression level of CD4(+)PD-1(+) and heart rate are potential risk factors while percentage of CD4(+) T cells is a possible protective factor for sepsis.
本研究旨在阐明程序性死亡受体1（PD-1）、T细胞免疫球蛋白黏蛋白分子3（Tim-3）和细胞毒性T淋巴细胞相关抗原4（CTLA-4）在脓毒症中的作用。
选取脓毒症患者182例作为脓毒症组，并分为三个亚组：轻度脓毒症组、重度脓毒症组和脓毒性休克组；选取185名健康志愿者作为对照组。对T淋巴细胞及表面共刺激分子表达进行流式细胞术检测及血常规检查。应用Pearson相关性检验分析脓毒症患者T淋巴细胞表面共刺激分子表达与危重病情况的相关性。对脓毒症的危险因素进行Logistic回归分析。
各亚组心率及白细胞计数均高于对照组（P<0.05）。各亚组急性生理与慢性健康状况评分系统II（APACHE II）、简化急性生理学评分II（SAP II）及序贯器官衰竭评估（SOFA）评分差异具有统计学意义（P<0.05）。与对照组相比，各亚组淋巴细胞比例及CD4(+)T细胞百分比降低（P<0.05）。CD4(+)PD-1(+)、CD8(+)PD-1(+)及CD8(+)CTLA-4(+)表达水平差异具有统计学意义（P<0.05）。显然，CD4(+)TIM-3(+)、CD8(+)TIM-3(+)、CD4(+)PD-1(+)、CD8(+)PD-1(+)及CD4(+)CTLA-4(+)表达水平与APACHE II评分呈正相关（均P<0.05）。Logistic回归分析显示，心率及CD4(+)PD-1(+)表达水平可能为脓毒症的危险因素，而CD4(+)T细胞百分比可能为脓毒症的保护因素（P<0.05）。
PD-1加重免疫反应，这与脓毒症中T细胞耗竭的促进作用一致。CD4(+)PD-1(+)表达水平及心率为脓毒症的潜在危险因素，而CD4(+)T细胞百分比可能为脓毒症的保护因素。
