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Rapamycin, and not cyclosporin A, preserves the highly suppressive CD27+ subset of human CD4+CD25+ regulatory T cells.
Blood. 2006 Feb 01; 107(3):1018-23.Blood

Abstract

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.

Authors+Show Affiliations

Department of Bloodtransfusion and Transplantation Immunology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16210336

Citation

Coenen, Jeroen J A., et al. "Rapamycin, and Not Cyclosporin A, Preserves the Highly Suppressive CD27+ Subset of Human CD4+CD25+ Regulatory T Cells." Blood, vol. 107, no. 3, 2006, pp. 1018-23.
Coenen JJ, Koenen HJ, van Rijssen E, et al. Rapamycin, and not cyclosporin A, preserves the highly suppressive CD27+ subset of human CD4+CD25+ regulatory T cells. Blood. 2006;107(3):1018-23.
Coenen, J. J., Koenen, H. J., van Rijssen, E., Hilbrands, L. B., & Joosten, I. (2006). Rapamycin, and not cyclosporin A, preserves the highly suppressive CD27+ subset of human CD4+CD25+ regulatory T cells. Blood, 107(3), 1018-23.
Coenen JJ, et al. Rapamycin, and Not Cyclosporin A, Preserves the Highly Suppressive CD27+ Subset of Human CD4+CD25+ Regulatory T Cells. Blood. 2006 Feb 1;107(3):1018-23. PubMed PMID: 16210336.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rapamycin, and not cyclosporin A, preserves the highly suppressive CD27+ subset of human CD4+CD25+ regulatory T cells. AU - Coenen,Jeroen J A, AU - Koenen,Hans J P M, AU - van Rijssen,Esther, AU - Hilbrands,Luuk B, AU - Joosten,Irma, Y1 - 2005/10/06/ PY - 2005/10/8/pubmed PY - 2006/3/3/medline PY - 2005/10/8/entrez SP - 1018 EP - 23 JF - Blood JO - Blood VL - 107 IS - 3 N2 - 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. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/16210336/Rapamycin_and_not_cyclosporin_A_preserves_the_highly_suppressive_CD27+_subset_of_human_CD4+CD25+_regulatory_T_cells_ L2 - https://ashpublications.org/blood/article-lookup/doi/10.1182/blood-2005-07-3032 DB - PRIME DP - Unbound Medicine ER -