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Critical Care
Published in: Critical Care 1/2011

Open Access 01-02-2011 | Research

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

Authors: Yan Zhang, Jinbao Li, Jingsheng Lou, Ying Zhou, Lulong Bo, Jiali Zhu, Keming Zhu, Xiaojian Wan, Zailong Cai, Xiaoming Deng

Published in: Critical Care | Issue 1/2011

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Abstract

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.
Appendix
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Metadata
Title
Upregulation of programmed death-1 on T cells and programmed death ligand-1 on monocytes in septic shock patients
Authors
Yan Zhang
Jinbao Li
Jingsheng Lou
Ying Zhou
Lulong Bo
Jiali Zhu
Keming Zhu
Xiaojian Wan
Zailong Cai
Xiaoming Deng
Publication date
01-02-2011
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2011
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc10059

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