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

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-gamma, IL-2 and TNF-alpha 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-gamma 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.