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Updated: Nov 15, 2025

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Packed red blood cells inhibit T-cell activation via ROS-dependent signaling pathways.

Marlene C Gerner1, Andrea Bileck2, Lukas Janker2

  • 1Division of Biomedical Science, University of Applied Sciences FH Campus Wien, Vienna, Austria; Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.

The Journal of Biological Chemistry
|March 7, 2021
PubMed
Summary

Packed red blood cells (PRBCs) inhibit T-cell activation by reducing reactive oxygen species production. This cell-cell contact-dependent mechanism impacts T-cell receptor signaling, potentially explaining transfusion-related immunomodulation.

Keywords:
T-cellerythrocyteimmunosuppressionphosphoproteomicsreactive oxygen speciesredox regulation

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Area of Science:

  • Immunology
  • Cell Biology
  • Hematology

Background:

  • Red blood cells (RBCs) are known to influence T-cell responses.
  • The precise mechanisms by which packed RBCs (PRBCs) modulate T-cell activation remain incompletely understood.

Purpose of the Study:

  • To investigate the effects of PRBCs on T-cell receptor (TCR) signaling.
  • To elucidate the molecular mechanisms underlying PRBC-mediated T-cell modulation.

Main Methods:

  • Studied T-cell activation markers (CD25, CD69) and proliferation in the presence of PRBCs.
  • Assessed TCR signaling, reactive oxygen species (ROS) production, and downstream phosphoproteomics.
  • Utilized direct cell-cell contact assays and compared PRBCs to antioxidants like N-acetyl cysteine.

Main Results:

  • PRBCs attenuated T-cell activation markers, proliferation, and cytokine expression.
  • Inhibitory effects required direct cell-cell contact and intact PRBCs.
  • PRBCs abrogated ROS production and affected downstream signaling pathways dependent on ROS, without impacting proximal TCR signaling.

Conclusions:

  • PRBCs modulate T-cell activation primarily by interfering with ROS-dependent signaling pathways.
  • This immunomodulatory effect, mediated by direct cell contact, may explain clinical observations following PRBC transfusion.
  • Inflammation-related radical reactions are implicated in PRBC-mediated immunomodulation.