[HTML][HTML] Upregulation of programmed death-1 on T cells and programmed death ligand-1 on monocytes in septic shock patients
Y Zhang, J Li, J Lou, Y Zhou, L Bo, J Zhu, K Zhu, X Wan… - Critical care, 2011 - Springer
Y Zhang, J Li, J Lou, Y Zhou, L Bo, J Zhu, K Zhu, X Wan, Z Cai, X Deng
Critical care, 2011•SpringerIntroduction 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 …
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 …
Introduction
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.
Methods
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 in vitro and effects of anti-PD-L1 antibody administration were measured by flow cytometry. CD14+ 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.
Results
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+ T cells, CD8+ T cells and CD19+ 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 in vitro 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 in vitro.
Conclusions
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.
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