Rapamycin, and not cyclosporin A, preserves the highly suppressive CD27+ subset of human CD4+CD25+ regulatory T cells
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The immunosuppressive drugs rapamycin and cyclosporin A (CsA) are widely used to prevent allograft rejection. Moreover, they were shown to be instrumental in experimental models of tolerance induction. However, it remains to be elucidated whether these drugs have an effect on the CD4+ CD25+ regulatory T-cell (T(REG)) population, which plays an important role in allograft tolerance. Recently, we reported that alloantigen-driven expansion of human CD4+ CD25+ T(REG)s gives rise to a distinct highly suppressive CD27+ T(REG) subset next to a moderately suppressive CD27- T(REG) subset. In the current study we found that rapamycin and CsA do not interfere with the suppressive activity of human naturally occurring CD4+ CD25+ T cells. However, in contrast to CsA, rapamycin preserved the dominance of the potent CD27+ T(REG) subset over the CD27- T(REG) subset after alloantigen-driven expansion of CD4+ CD25+ T(REG)s in vitro. Accordingly, CD4+ CD25+ T(REG)s cultured in the presence of rapamycin displayed much stronger suppressive capacity than CD4+ CD25+ T(REG)s cultured in the presence of CsA. In addition, CD4+ CD25+ T(REG) cells cultured in the presence of rapamycin, but not CsA, were able to suppress ongoing alloimmune responses. This differential effect of rapamycin and CsA on the CD27+ T(REG) subset dominance may favor the use of rapamycin in tolerance-inducing strategies.
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Sirolimus has been shown to selectively preserve the development of regulatory T cells.
“and has also been shown to selectively preserve the development of Tregs, 172”
From Autoimmune diseases and immune-checkpoint inhibitors for cancer therapy: Review of the literature and personalized risk-based prevention strategy (2020) · cites this paper as [172]
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- Authors
- Coenen, J. J. A., Koenen, H. J. P. M., van Rijssen, E., Hilbrands, L. B., & Joosten, I.
- Affiliations
- Radboud University Medical Center (NL)
- From the Department of Bloodtransfusion and Transplantation Immunology and the Department of Nephrology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2006-02-01
- Volume
- 107
- Issue
- 3
- Pages
- 1018-1023
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1972290737
- Cited by
- 252
- References
- 38
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 2 · 2021: 5 · 2020: 6 · 2019: 4 · 2018: 4 · 2017: 14 · 2016: 9 · 2015: 13 · 2014: 14 · 2013: 8 · 2012: 21
- FWCI
- 8.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Nierstichting
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Transplantation › Renal Transplantation Outcomes and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- rapamycin, cyclosporine, regulatory T cells, CD4+CD25+ T cells, immunosuppressants, allograft tolerance, suppressor activity, mTOR inhibition
- MeSH terms
- Cells, Cultured, Dose-Response Relationship, Drug, Graft Rejection, Humans, Immune Tolerance, Immunosuppressive Agents, Isoantigens, Lymphocyte Activation, Transplantation, Homologous, Cyclosporine, Tumor Necrosis Factor Receptor Superfamily, Member 7, Sirolimus, T-Lymphocytes, Regulatory
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