Upregulation of programmed death-1 on T cells and programmed death ligand-1 on monocytes in septic shock patients

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Introduction</jats:title> <jats:p>Studies on the role of programmed death-1(PD-1) and its main ligand (PD-L1) during experimental models of sepsis have shown that the PD-1/PD-L1 pathway plays a pathologic role in altering microbial clearance, the innate inflammatory response and accelerated apoptosis in sepsis. However, the expression of PD-1 and PD-L1 and their role during the development of immune suppression in septic patients have not been elucidated. The present study was designed to determine whether the expression of PD-1 and PD-L1 is upregulated in septic shock patients and to explore the role of this pathway in sepsis-induced immunosuppression.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>Nineteen septic shock patients and 22 sex-matched and age-matched healthy controls were prospectively enrolled. Apoptosis in lymphocyte subpopulations and PD-1/PD-L1 expression on peripheral T cells, B cells and monocytes were measured using flow cytometry. Apoptosis of T cells induced by TNFα or T-cell receptor ligation <jats:italic>in vitro</jats:italic> and effects of anti-PD-L1 antibody administration were measured by flow cytometry. CD14<jats:sup>+</jats:sup> monocytes of septic shock patients were purified and incubated with either lipopolysaccharide, anti-PD-L1 antibody, isotype antibody, or a combination of lipopolysaccharide and anti-PD-L1 antibody or isotype antibody. Supernatants were harvested to examine production of cytokines by ELISA.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Compared with healthy controls, septic shock induced a marked increase in apoptosis as detected by the annexin-V binding and active caspase-3 on CD4<jats:sup>+</jats:sup> T cells, CD8<jats:sup>+</jats:sup> T cells and CD19<jats:sup>+</jats:sup> B cells. Expression of PD-1 on T cells and of PD-L1 on monocytes was dramatically upregulated in septic shock patients. PD-1/PD-L1 pathway blockade <jats:italic>in vitro</jats:italic> with anti-PD-L1 antibody decreased apoptosis of T cells induced by TNFα or T-cell receptor ligation. Meanwhile, this blockade potentiated the lipopolysaccharide-induced TNFα and IL-6 production and decreased IL-10 production by monocytes <jats:italic>in vitro</jats:italic>.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>The expression of PD-1 on T cells and PD-L1 on monocytes was upregulated in septic shock patients. The PD-1/PD-L1 pathway might play an essential role in sepsis-induced immunosuppression.</jats:p> </jats:sec>