Increased Expression of Programmed Cell Death-1 in Regulatory T Cells of Patients with Severe Sepsis and Septic Shock: An Observational Clinical Study.

While regulatory T cells (Tregs) constitutively express programmed cell death-1 (PD-1), the role of PD-1 expression in Tregs of patients with sepsis remains unclear. Thus, we determined PD-1 expression in Tregs from the peripheral blood of patients with severe sepsis and septic shock. Seventy-eight patients with severe sepsis and 40 with septic shock, as well as 21 healthy subjects, were enrolled in this study. The percentage of peripheral blood PD-1+ Tregs, as well as absolute Treg counts, were compared between these three groups. PD-1 expression in Tregs and absolute Treg counts were also compared between survivors and non-survivors in patients with sepsis. PD-1 expression in Tregs increased in patients with sepsis compared to healthy controls. Conversely, absolute Treg counts were significantly decreased in patients with sepsis compared to healthy controls; patients with septic shock had the lowest absolute Treg counts. Among patients with sepsis, survivors had lower levels of PD-1 expression in Tregs, as well as higher absolute Treg counts, than non-survivors. Additionally, the percentage of PD-1+ Tregs correlated positively with lactate levels as well as the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores in patients with sepsis. PD-1 was upregulated in Tregs of patients with sepsis and may indicate a state of immune dysfunction. Overexpression of PD-1 in Tregs was associated with more severe sepsis as well as poor outcomes.