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Packed red blood cells inhibit T-cell activation via ROS-dependent signaling pathways.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2021 Jan-Jun; Vol. 296, pp. 100487. Date of Electronic Publication: 2021 Mar 04. - Publication Year :
- 2021
-
Abstract
- Numerous observations indicate that red blood cells (RBCs) affect T-cell activation and proliferation. We have studied effects of packed RBCs (PRBCs) on T-cell receptor (TCR) signaling and the molecular mechanisms whereby (P)RBCs modulate T-cell activation. In line with previous reports, PRBCs attenuated the expression of T-cell activation markers CD25 and CD69 upon costimulation via CD3/CD28. In addition, T-cell proliferation and cytokine expression were markedly reduced when T-cells were stimulated in the presence of PRBCs. Inhibitory activity of PRBCs required direct cell-cell contact and intact PRBCs. The production of activation-induced cellular reactive oxygen species, which act as second messengers in T-cells, was completely abrogated to levels of unstimulated T-cells in the presence of PRBCs. Phosphorylation of the TCR-related zeta chain and thus proximal TCR signal transduction was unaffected by PRBCs, ruling out mechanisms based on secreted factors and steric interaction restrictions. In large part, downstream signaling events requiring reactive oxygen species for full functionality were affected, as confirmed by an untargeted MS-based phosphoproteomics approach. PRBCs inhibited T-cell activation more efficiently than treatment with 1 mM of the antioxidant N-acetyl cysteine. Taken together, our data imply that inflammation-related radical reactions are modulated by PRBCs. These immunomodulating effects may be responsible for clinical observations associated with transfusion of PRBCs.<br />Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.<br /> (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Antigens, CD metabolism
Antigens, Differentiation, T-Lymphocyte metabolism
Cell Proliferation physiology
Cells, Cultured
Erythrocytes metabolism
Humans
Immunomodulation
Interleukin-2 Receptor alpha Subunit metabolism
Lectins, C-Type metabolism
Leukocytes, Mononuclear
Lymphocyte Activation
Phosphorylation
Signal Transduction
T-Lymphocytes metabolism
Antigens, CD immunology
Antigens, Differentiation, T-Lymphocyte immunology
Erythrocytes immunology
Interleukin-2 Receptor alpha Subunit immunology
Lectins, C-Type immunology
Reactive Oxygen Species metabolism
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 296
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 33676898
- Full Text :
- https://doi.org/10.1016/j.jbc.2021.100487