Expression of PD-1 on Memory T Lymphocytes Predicts 28-Day Mortality of Patients with Sepsis: A Prospective Observational Study

Abstract

Qingxiang Liu,1 Ming Xue,1 Qianwen Song,1 Jianfeng Xie,1 Yi Yang,1 Songqiao Liu1,2 1Jiangsu 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; 2Department of Critical Care Medicine, Nanjing Lishui People’s Hospital, Zhongda Hospital Lishui Branch, Nanjing, People’s Republic of ChinaCorrespondence: Yi Yang; Songqiao Liu, Email [email protected]; [email protected]: 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 (P=0.617) or naive CD8+ T cells (P=0.079) between survivors (n = 21) and nonsurvivors (n = 9). Increased PD-1 expression on memory CD4+ T cells was found in nonsurvivors (P=0.030) and memory CD8+ T cells (P=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 (P=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 (P=0.046) and IL-2 secretion of memory CD8+ T cells (P=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.Keywords: PD-1, memory T cells, sepsis, outcome

Keywords

• pd-1
• memory t cells
• sepsis
• outcome