记忆性T淋巴细胞上PD-1的表达可预测脓毒症患者的28天死亡率：一项前瞻性观察研究。
Expression of PD-1 on Memory T Lymphocytes Predicts 28-Day Mortality of Patients with Sepsis: A Prospective Observational Study.
作者信息
Liu Qingxiang, Xue Ming, Song Qianwen, Xie Jianfeng, Yang Yi, Liu Songqiao
机构信息
Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People's Republic of China.
Department of Critical Care Medicine, Nanjing Lishui People's Hospital, Zhongda Hospital Lishui Branch, Nanjing, People's Republic of China.
出版信息
J Inflamm Res. 2022 Sep 1;15:5043-5052. doi: 10.2147/JIR.S376897. eCollection 2022.
BACKGROUND
PD-1 is an important immune checkpoint expressed on T lymphocytes and is associated with T-cell function in sepsis. However, the role of PD-1 in naive and memory T-cell responses in sepsis is not well understood. We aimed to determine the expression of PD-1 induced on naive and memory T lymphocytes in patients with sepsis and its association with clinical outcome.
METHODS
A prospective observational study was conducted at a general intensive care unit (ICU). Whole blood samples were collected from patients within 48 h after sepsis diagnosis. PD-1 expression on naive and memory T cells was measured by flow cytometry. The levels of IFN-γ, IL-2 and TNF-α released by memory T cells were also determined. All patients were followed up to 28 days, and 28-day mortality was recorded.
RESULTS
PD-1 expression showed no difference in naive CD4 T cells (=0.617) or naive CD8 T cells (=0.079) between survivors (n = 21) and nonsurvivors (n = 9). Increased PD-1 expression on memory CD4 T cells was found in nonsurvivors (=0.030) and memory CD8 T cells (=0.006) in comparison with survivors. According to the cutoff value of the percentage of PD-1 on memory CD8 T cells in predicting 28-day mortality of patients with sepsis, patients were divided into two groups. The 28-day mortality rates between the two groups were significantly different (=0.009). A Kaplan Meier curve was constructed to derive a hazard ratio of 9.33 (95% CI: 2.52-34.60) for the percentage of PD-1 on memory CD8 T cells regarding 28-day mortality. In addition, the IFN-γ secretion of memory CD4 T cells (=0.046) and IL-2 secretion of memory CD8 T cells (=0.014) were significantly greater in survivors than nonsurvivors.
CONCLUSION
Flow cytometric assessment of PD-1 expression on memory CD8 T cells identifies patients with poor outcomes during sepsis.
背景
程序性死亡受体1（PD-1）是一种在T淋巴细胞上表达的重要免疫检查点，与脓毒症中的T细胞功能相关。然而，PD-1在脓毒症中初始T细胞和记忆T细胞反应中的作用尚不清楚。我们旨在确定脓毒症患者初始T淋巴细胞和记忆T淋巴细胞上诱导的PD-1表达及其与临床结局的关系。
方法
在一家综合重症监护病房（ICU）进行了一项前瞻性观察性研究。在脓毒症诊断后48小时内从患者采集全血样本。通过流式细胞术测量初始T细胞和记忆T细胞上的PD-1表达。还测定了记忆T细胞释放的干扰素-γ（IFN-γ）、白细胞介素-2（IL-2）和肿瘤坏死因子-α（TNF-α）水平。对所有患者进行28天随访，并记录28天死亡率。
结果
存活者（n = 21）和非存活者（n = 9）之间，初始CD4 T细胞（P = 0.617）或初始CD8 T细胞（P = 0.079）上的PD-1表达无差异。与存活者相比，非存活者记忆CD4 T细胞（P = 0.030）和记忆CD8 T细胞（P = 0.006）上的PD-1表达增加。根据记忆CD8 T细胞上PD-1百分比预测脓毒症患者28天死亡率的临界值，将患者分为两组。两组之间的28天死亡率有显著差异（P = 0.009）。构建了一条Kaplan Meier曲线，得出记忆CD8 T细胞上PD-1百分比关于28天死亡率的风险比为9.33（95%置信区间：2.52 - 34.60）。此外，存活者记忆CD4 T细胞的IFN-γ分泌（P = 0.046）和记忆CD8 T细胞的IL-2分泌（P = 0.014）显著高于非存活者。
结论
通过流式细胞术评估记忆CD8 T细胞上的PD-1表达可识别脓毒症期间预后不良的患者。
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