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Myeloid-Derived Suppressor Cells Mediate Immunosuppression After Cardiopulmonary Bypass
- Source :
- Critical Care Medicine. 47:e700-e709
- Publication Year :
- 2019
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2019.
-
Abstract
- Objectives Cardiopulmonary bypass is associated with severe immune dysfunctions. Particularly, a cardiopulmonary bypass-related long-lasting immunosuppressive state predisposes patients to a higher risk of postoperative complications, such as persistent bacterial infections. This study was conducted to elucidate mechanisms of post-cardiopulmonary bypass immunosuppression. Design In vitro studies with human peripheral blood mononuclear cells. Setting Cardiosurgical ICU, University Research Laboratory. Patients Seventy-one patients undergoing cardiac surgery with cardiopulmonary bypass (enrolled May 2017 to August 2018). Interventions Peripheral blood mononuclear cells before and after cardiopulmonary bypass were analyzed for the expression of immunomodulatory cell markers by real-time quantitative reverse transcription polymerase chain reaction. T cell effector functions were determined by enzyme-linked immunosorbent assay, carboxyfluorescein succinimidyl ester staining, and cytotoxicity assays. Expression of cell surface markers was assessed by flow cytometry. CD15 cells were depleted by microbead separation. Serum arginine was measured by mass spectrometry. Patient peripheral blood mononuclear cells were incubated in different arginine concentrations, and T cell functions were tested. Measurements and main results After cardiopulmonary bypass, peripheral blood mononuclear cells exhibited significantly reduced levels of costimulatory receptors (inducible T-cell costimulator, interleukin 7 receptor), whereas inhibitory receptors (programmed cell death protein 1 and programmed cell death 1 ligand 1) were induced. T cell effector functions (interferon γ secretion, proliferation, and CD8-specific cell lysis) were markedly repressed. In 66 of 71 patients, a not yet described cell population was found, which could be characterized as myeloid-derived suppressor cells. Myeloid-derived suppressor cells are known to impair immune cell functions by expression of the arginine-degrading enzyme arginase-1. Accordingly, we found dramatically increased arginase-1 levels in post-cardiopulmonary bypass peripheral blood mononuclear cells, whereas serum arginine levels were significantly reduced. Depletion of myeloid-derived suppressor cells from post-cardiopulmonary bypass peripheral blood mononuclear cells remarkably improved T cell effector function in vitro. Additionally, in vitro supplementation of arginine enhanced T cell immunocompetence. Conclusions Cardiopulmonary bypass strongly impairs the adaptive immune system by triggering the accumulation of myeloid-derived suppressor cells. These myeloid-derived suppressor cells induce an immunosuppressive T cell phenotype by increasing serum arginine breakdown. Supplementation with L-arginine may be an effective measure to counteract the onset of immunoparalysis in the setting of cardiopulmonary bypass.
- Subjects :
- Male
Neutrophils
T-Lymphocytes
T cell
Enzyme-Linked Immunosorbent Assay
Adaptive Immunity
Critical Care and Intensive Care Medicine
Peripheral blood mononuclear cell
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Immune system
Humans
Medicine
Interleukin-7 receptor
Heart Failure
Cardiopulmonary Bypass
Cluster of differentiation
business.industry
Myeloid-Derived Suppressor Cells
030208 emergency & critical care medicine
Carboxyfluorescein succinimidyl ester
Middle Aged
Flow Cytometry
Acquired immune system
medicine.anatomical_structure
030228 respiratory system
chemistry
Leukocytes, Mononuclear
Cancer research
Myeloid-derived Suppressor Cell
Female
business
Subjects
Details
- ISSN :
- 00903493
- Volume :
- 47
- Database :
- OpenAIRE
- Journal :
- Critical Care Medicine
- Accession number :
- edsair.doi.dedup.....332a1d52f4e55ffacb875133e2ab5090