MONOCYTIC MYELOID-DERIVED SUPPRESSOR CELL EXPANSION AFTER CARDIAC SURGERY WITH CARDIOPULMONARY BYPASS INDUCES
Mathieu Lesouhaitier, Fabrice Uhel, Murielle Gregoire
1Service d'Anesthésie-Réanimation, CHU Rennes, Rennes, France.
Insights
Cardiac surgery with cardiopulmonary bypass (CPB) causes immune suppression via myeloid-derived suppressor cells (MDSCs), leading to reduced T-cell function. Arginine supplementation partially restored T-cell proliferation after CPB.
Area of Science:
- Immunology
- Surgical Science
- Cellular Biology
Background:
- Cardiopulmonary bypass (CPB) in cardiac surgery induces immune paresis, increasing infection risk.
- Myeloid-derived suppressor cells (MDSCs) are implicated in CPB-induced immunosuppression by promoting lymphocyte apoptosis and inhibiting proliferation.
- The precise mechanisms underlying CPB-induced immunosuppression mediated by MDSCs require further elucidation.
Purpose of the Study:
- To investigate the impact of CPB on lymphocyte subsets and T-cell function.
- To identify the role of monocytic and granulocytic MDSCs in CPB-induced immunosuppression.
- To explore the mechanisms, including indoleamine 2,3-dioxygenase (IDO), IL-10, programmed death-ligand 1 (PD-L1), and arginine, involved in CPB-induced T-cell dysfunction.
Main Methods:
- Analysis of lymphocyte subsets 24 hours post-CPB.
- Assessment of T-cell apoptosis and proliferation capacity ex vivo.
- Quantification of monocytic and granulocytic MDSC populations.
- Measurement of plasma levels of IDO, IL-10, PD-L1, and arginine.
- Evaluation of interventions including MDSC depletion, IDO inhibition, anti-PD-L1/IL-10 antibodies, and arginine supplementation.
Main Results:
- CPB significantly decreased main lymphocyte subsets and expanded monocytic MDSCs, correlating with increased T-cell apoptosis and reduced proliferation.
- Granulocytic MDSCs remained stable, while MDSC depletion restored ex vivo T-cell proliferation.
- Post-CPB, elevated IDO activity, IL-10, and PD-L1 expression were observed, alongside decreased arginine levels.
Conclusions:
- Monocytic MDSCs play a critical role in CPB-induced T-cell dysfunction following cardiac surgery.
- Arginine deficiency, rather than IDO, IL-10, or PD-L1, appears to be a key factor limiting T-cell proliferation post-CPB.
- Arginine supplementation offers a potential therapeutic strategy to partially restore T-cell function after CPB.
Abstract:
Cardiac surgery with cardiopulmonary bypass (CPB) is associated with an immune paresis that predisposes to the development of postoperative infections and sepsis. Among factors responsible for CPB-induced immunosuppression, circulating myeloid-derived suppressor cells (MDSCs) have been found to induce early lymphocyte apoptosis and lymphocyte proliferation inhibition. However, the mechanisms involved are not fully understood. In this study, we found that the main lymphocyte subsets decreased significantly 24 h after cardiac surgery with CBP. As expected, cardiac surgery with CPB induced a monocytic MDSC expansion associated with an increased T-cell apoptosis and decreased proliferation capacity. Noteworthy, granulocytic MDSCs remain stable. Myeloid-derived suppressor cell depletion restored the ability of T-cell to proliferate ex vivo . After CPB, indoleamine 2,3-dioxygenase activity and IL-10 plasma level were increased such as programmed death-ligand 1 monocytic expression, whereas plasma level of arginine significantly decreased. Neither the inhibition of indoleamine 2,3-dioxygenase activity nor the use of anti-programmed death-ligand 1 or anti-IL-10 blocking antibody restored the ability of T-cell to proliferate ex vivo . Only arginine supplementation restored partially the ability of T-cell to proliferate.
