T ‐cell suppression by red blood cells is dependent on intact cells and is a consequence of blood bank processing
Open accessAbstract
Background: Red blood cells ( RBC s) suppress T ‐cell responsiveness through a mechanism requiring cell–cell contact. Questions remain as to whether this effect is an allogeneic response, related to cell death, or dependent on particular components of the RBC s. Study Design and Methods: Peripheral T cells were isolated from healthy donors and exposed to stored allogeneic RBCs or autologous RBC s after processing. RBC s were lysed by hypotonic solvent to produce cellular ghosts. Tritiated thymidine proliferation assays were utilized. Cultures were saturated with interleukin ( IL )‐2 to determine whether impaired IL ‐2 synthesis played a role. Results: T ‐cell proliferation was suppressed by both autologous and allogeneic RBCs . RBC membrane integrity does enhance T ‐cell suppression. T ‐cell death is not responsible for the suppressive changes. IL ‐2 synthesis is suppressed in RBC ‐exposed T cells but addition of exogenous IL ‐2 does not rescue proliferative capabilities. Proliferation of T cells was inhibited with RBC exposure but mitigated with the addition of fresh RBCs . Conclusions: T ‐cell suppression is enhanced by intact RBCs but this effect is unrelated solely to alloantigens. Neither apoptosis nor necrosis of T cells contributes to this phenomenon. IL ‐2 synthesis is suppressed after RBC exposure as a consequence of T ‐cell inhibition, but is not the primary cause of suppression. Fresh RBCs do not mediate T ‐cell suppression, indicating that changes in the RBC and development of the storage lesion may occur during initial blood bank processing.
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The presence of MDSCs and monocytes can hamper the ex vivo activation and expansion of T cells, and other contaminants such as granulocytes and red blood cells suppress T cell proliferation.
“The presence of MDSCs and monocytes can hamper the ex vivo activation and expansion of T cells (40,42-44). Other cellular contaminants such as granulocytes and red blood cells suppress T cell proliferation (45,46).”
From Scalable Manufacturing of CAR T Cells for Cancer Immunotherapy (2021) · cites this paper as [45]
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- Authors
- Long, K., Meier, C., Bernard, A., Williams, D., Davenport, D., & Woodward, J.
- Affiliations
- University of Kentucky (US)
- Corresponding author
- Long, Kristin
- Venue
- Transfusion
- Publisher
- Wiley
- Published
- 2013-11-04
- Volume
- 54
- Issue
- 5
- Pages
- 1340-1347
- ISSN
- 0041-1132 (ISSN-L)
- 1537-2995
- PMC
- PMC4344125
- OpenAlex
- W1528769634
- Cited by
- 29
- References
- 24
- Citations by year
- 2026: 4 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 1 · 2020: 2 · 2019: 5 · 2018: 3 · 2017: 4 · 2016: 1 · 2014: 1
- FWCI
- 0.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Transfusion (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000117)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Biochemistry › Blood transfusion and management
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Hematology › Blood groups and transfusion
- Keywords
- T cell suppression, storage lesion, erythrocyte ghosts, T cell proliferation, cell-cell contact, autologous red blood cells, T cell apoptosis
- MeSH terms
- Blood Banks, Cells, Cultured, Erythrocytes, Humans, Immune Tolerance, Interleukin-2, Lymphocyte Activation, T-Lymphocytes, Apoptosis
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