Cited by 254T-cell and B-cell ImmunologyRenal Transplantation Outcomes and TreatmentsSignaling Pathways in Disease

The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.

Rapamycin, and not cyclosporin A, preserves the highly suppressive CD27+ subset of human CD4+CD25+ regulatory T cells

Open access

Coenen, Jeroen J. A., Koenen, Hans J. P. M., van Rijssen, Esther, Hilbrands, Luuk B., Joosten, Irma·2006·Blood

DOI 10.1182/blood-2005-07-3032

Open this paper in CoChat — free account Open PDF

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1182/blood-2005-07-3032

Cites

38 of 38 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

CD4+CD25+ suppressor T cells: more questions than answers
Shevach, E. M. (2002) · Nature reviews. Immunology · doi:10.1038/nri821 · Cited by 2,097
Regulatory T cells in transplantation tolerance
Wood, K. J., & Sakaguchi, S. (2003) · Nature reviews. Immunology · doi:10.1038/nri1027 · Cited by 1,319
CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation
Edinger, M., Hoffmann, P., Ermann, J., Drago, K., Fathman, C. G., Strober, S., & Negrin, R. S. (2003) · Nature Medicine · doi:10.1038/nm915 · Cited by 1,286
In Vitro–expanded Antigen-specific Regulatory T Cells Suppress Autoimmune Diabetes
Tang, Q., Henriksen, K., Bi, M., Finger, E. B., Szot, G. L., Ye, J., Masteller, E. L., McDevitt, H. O., Bonyhadi, M. L., & Bluestone, J. A. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040139 · Cited by 1,232
Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells.
Battaglia, M., Stabilini, A., & Roncarolo, M. (2005) · Blood · doi:10.1182/blood-2004-10-3932 · Cited by 1,203
Co-stimulatory members of the TNFR family: keys to effective T-cell immunity?
Croft, M. (2003) · Nature reviews. Immunology · doi:10.1038/nri1148 · Cited by 863
Blocking both signal 1 and signal 2 of T-cell activation prevents apoptosis of alloreactive T cells and induction of peripheral allograft tolerance
Li, Y.-S., Li, X.-C., Zheng, X., Wells, A., Turka, L., & Strom, T. (1999) · Nature Medicine · doi:10.1038/15256 · Cited by 830
Tolerance, not immunity, crucially depends on IL-2
Malek, T. R., & Bayer, A. L. (2004) · Nature reviews. Immunology · doi:10.1038/nri1435 · Cited by 819
IL-10 Is Required for Regulatory T Cells to Mediate Tolerance to Alloantigens In Vivo
Hara, M., Kingsley, C. I., Niimi, M., Read, S., Turvey, S. E., Bushell, A., Morris, P. J., Powrie, F. M., & Wood, K. J. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.6.3789 · Cited by 765
CD25+CD4+ Regulatory T Cells Prevent Graft Rejection: CTLA-4- and IL-10-Dependent Immunoregulation of Alloresponses
Kingsley, C. I., Karim, M., Bushell, A., & Wood, K. J. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.3.1080 · Cited by 742
Two distinct signal transmission pathways in T lymphocytes are inhibited by complexes formed between an immunophilin and either FK506 or rapamycin.
Bierer, B. E., Mattila, P. S., Standaert, R. F., Herzenberg, L. A., Burakoff, S. J., Crabtree, G. R., & Schreiber, S. L. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.23.9231 · Cited by 706
IMMUNOPHARMACOLOGY OF RAPAMYCIN
Abraham, R. T., & Wiederrecht, G. (1996) · Annual Review of Immunology · doi:10.1146/annurev.immunol.14.1.483 · Cited by 653
Interleukin 2 Signaling Is Required for CD4+ Regulatory T Cell Function
Furtado, G. C., de Lafaille, M. A. C., Kutchukhidze, N., & Lafaille, J. J. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20020190 · Cited by 625
Requirement for T-cell apoptosis in the induction of peripheral transplantation tolerance
Wells, A. D., Li, X. C., Li, Y., Walsh, M. C., Zheng, X. X., Wu, Z., Núñez, G., Tang, A., Sayegh, M. H., Hancock, W. W., et al. (1999) · Nature Medicine · doi:10.1038/15260 · Cited by 595
Identification of Regulatory T Cells in Tolerated Allografts
Graça, L., Cobbold, S. P., & Waldmann, H. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20012097 · Cited by 566
Recipient-type specific CD4+CD25+ regulatory T cells favor immune reconstitution and control graft-versus-host disease while maintaining graft-versus-leukemia
Trenado, A., Charlotte, F., Fisson, S., Yagello, M., Klatzmann, D., Salomon, B. L., & Cohen, J. L. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17702 · Cited by 493
Large-scale in vitro expansion of polyclonal human CD4+CD25high regulatory T cells
Hoffmann, P., Eder, R., Kunz‐Schughart, L. A., Andreesen, R., & Edinger, M. (2004) · Blood · doi:10.1182/blood-2004-01-0086 · Cited by 489
Coexpression of CD25 and CD27 identifies FoxP3+ regulatory T cells in inflamed synovia
Ruprecht, C. R., Gattorno, M., Ferlito, F., Gregorio, A., Martini, A., Lanzavecchia, A., & Sallusto, F. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050085 · Cited by 360
Activation requirements for the induction of CD4+CD25+ T cell suppressor function
Thornton, A. M., Piccirillo, C. A., & Shevach, E. M. (2004) · European Journal of Immunology · doi:10.1002/eji.200324455 · Cited by 297
Specific unresponsiveness in rats with prolonged cardiac allograft survival after treatment with cyclosporine. III. Further characterization of the CD4+ suppressor cell and its mechanisms of action.
Hall, B. M., PEARCE, N. W., Gurley, K. E., & Dorsch, S. E. (1990) · The Journal of Experimental Medicine · doi:10.1084/jem.171.1.141 · Cited by 297
Cord blood CD4+CD25+-derived T regulatory cell lines express FoxP3 protein and manifest potent suppressor function
Godfrey, W. R., Spoden, D. J., Ge, Y. G., Baker, S. R., Liu, B., Levine, B. L., June, C. H., Blazar, B. R., & Porter, S. B. (2004) · Blood · doi:10.1182/blood-2004-06-2467 · Cited by 297
Favorably Tipping the Balance between Cytopathic and Regulatory T Cells to Create Transplantation Tolerance
Zheng, X. X., Fueyo, A. S., Sho, M., Domenig, C. M., Sayegh, M. H., & Strom, T. B. (2003) · Immunity · doi:10.1016/s1074-7613(03)00259-0 · Cited by 248
The influence of immunosuppressive drugs on tolerance induction through bone marrow transplantation with costimulation blockade
Blaha, P., Bigenzahn, S., Koporc, Z., Schmid, M. P., Langer, F. B., Selzer, E., Bergmeister, H., Wrba, F., Kurtz, J. M., Kiss, C., et al. (2003) · Blood · doi:10.1182/blood-2002-10-3014 · Cited by 175
DIFFERENTIAL EFFECTS OF CYCLOSPORINE A, METHYLPREDNISOLONE, MYCOPHENOLATE, AND RAPAMYCIN ON CD154 INDUCTION AND REQUIREMENT FOR NF??B
Smiley, S. T., Csizmadia, V., Gao, W., Turka, L. A., & Hancock, W. W. (2000) · Transplantation · doi:10.1097/00007890-200008150-00005 · Cited by 154
Prevention of kidney allograft rejection using anti-CD40 and anti-CD86 in primates
Haanstra, K. G., Ringers, J., Sick, E. A., Ramdien‐Murli, S., Kuhn, E.-M., Boon, L., & Jonker, M. (2003) · Transplantation · doi:10.1097/01.tp.0000054835.58014.c2 · Cited by 125
The balance of deletion and regulation in allograft tolerance
Zheng, X. X., Fueyo, A. S., Domenig, C. M., & Strom, T. B. (2003) · Immunological Reviews · doi:10.1046/j.1600-065x.2003.00089.x · Cited by 105
CD27/CFSE-Based Ex Vivo Selection of Highly Suppressive Alloantigen-Specific Human Regulatory T Cells
Koenen, H. J. P. M., Fasse, E., & Joosten, I. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.12.7573 · Cited by 104
Self-citation
Renal allograft rejection is prevented by adoptive transfer of anergic T cells in nonhuman primates
Bashuda, H., Kimikawa, M., Seino, K., Kato, Y., Ono, F., Shimizu, A., Yagita∥, H., Teraoka, S., & Okumura, K. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23743 · Cited by 99
Regulation of expression of CD27, a T cell-specific member of a novel family of membrane receptors
de Jong, R., Loenen, W. A. M., Brouwer, M. C., van Emmerik, L., de Vries, E. F., Borst, J. G., & van Lier, R. A. W. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.146.8.2488 · Cited by 95
Everolimus and Basiliximab Permit Suppression by Human CD4+CD25+ Cells in vitro
Game, D. S., Hernández-Fuentes, M. P., & Lechler, R. I. (2005) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2005.00758.x · Cited by 95
New Insights Into the Interactions Between T-Cell Costimulatory Blockade and Conventional Immunosuppressive Drugs
Sho, M., Sandner, S. E., Najafian, N., Salama, A. D., Dong, V. M., Yamada, A., Kishimoto, K., Harada, H., Schmitt, I. G., & Sayegh, M. H. (2002) · Annals of Surgery · doi:10.1097/00000658-200211000-00018 · Cited by 92
Inhibitory and Stimulatory Effects of Cyclosporine A on the Development of Regulatory T Cells In Vivo
Kawai, M., Kitade, H., Mathieu, C., Waer, M., & Pirenne, J. (2005) · Transplantation · doi:10.1097/01.tp.0000153505.73700.32 · Cited by 84
Alloreactive T Cell Responses and Acute Rejection of Single Class II MHC-Disparate Heart Allografts Are under Strict Regulation by CD4+CD25+ T Cells
Schenk, S., Kish, D. D., He, C., El-Sawy, T., Chiffoleau, E., Chen, C., Wu, Z., Sandner, S. E., Gorbachev, A. V., Fukamachi, K., et al. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.6.3741 · Cited by 82
IL-15 and Cognate Antigen Successfully Expand De Novo-Induced Human Antigen-Specific Regulatory CD4+ T Cells That Require Antigen-Specific Activation for Suppression
Koenen, H. J. P. M., Fasse, E., & Joosten, I. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.12.6431 · Cited by 75
Self-citation
Superior T-cell suppression by rapamycin and FK506 over rapamycin and cyclosporine A because of abrogated cytotoxic T-lymphocyte induction, impaired memory responses, and persistent apoptosis
Koenen, H. J. P. M., Michielsen, E. C. H. J., Verstappen, J., Fasse, E., & Joosten, I. (2003) · Transplantation · doi:10.1097/01.tp.0000053752.87383.67 · Cited by 57
Self-citation
A novel CD154 monoclonal antibody in acute and chronic rat vascularized cardiac allograft rejection1
Yuan, X., Dong, V. M., Coito, A. J., Waaga, A. M., Salama, A. D., Benjamin, C. D., Sayegh, M. H., & Chandraker, A. K. (2002) · Transplantation · doi:10.1097/00007890-200206150-00008 · Cited by 26
Tolerizing Effects of Co-stimulation Blockade Rest on Functional Dominance of CD4+CD25+ Regulatory T Cells
Coenen, J. J. A., Koenen, H. J. P. M., van Rijssen, E., Hilbrands, L. B., & Joosten, I. (2005) · Transplantation · doi:10.1097/01.tp.0000147460.93587.87 · Cited by 24
Self-citation
Cyclosporine Preserves the Anergic State of Human T Cells Induced by Costimulation Blockade In Vitro
Koenen, H. J. P. M., Fasse, E., & Joosten, I. (2005) · Transplantation · doi:10.1097/01.tp.0000172217.97072.54 · Cited by 11
Self-citation

Sorted by citations

Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics
Brunstein, C. G., Miller, J. S., Cao, Q., McKenna, D. H., Hippen, K. L., Curtsinger, J., DeFor, T. E., Levine, B. L., June, C. H., Rubinstein, P., et al. (2010) · Blood · doi:10.1182/blood-2010-07-293795 · Cited by 1,052
Immunoregulatory functions of mTOR inhibition
Thomson, A. W., Turnquist, H. R., & Raimondi, G. (2009) · Nature reviews. Immunology · doi:10.1038/nri2546 · Cited by 873
Rapamycin Promotes Expansion of Functional CD4+CD25+FOXP3+ Regulatory T Cells of Both Healthy Subjects and Type 1 Diabetic Patients
Battaglia, M., Stabilini, A., Migliavacca, B., Horejs‐Hoeck, J., Kaupper, T., & Roncarolo, M. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.12.8338 · Cited by 746
Risk factors for acute GVHD and survival after hematopoietic cell transplantation
Jagasia, M., Arora, M., Flowers, M. E. D., Chao, N. J. A., McCarthy, P. L., Cutler, C. S., Urbano-Ispizúa, Á., Pavletic, S. Z., Haagenson, M. D., Zhang, M., et al. (2011) · Blood · doi:10.1182/blood-2011-06-364265 · Cited by 706
Inhibition of CD4+CD25+ regulatory T-cell function by calcineurin-dependent interleukin-2 production
Zeiser, R., Nguyen, V. H., Beilhack, A., Buess, M., Schulz, S., Baker, J. B., Contag, C. H., & Negrin, R. S. (2006) · Blood · doi:10.1182/blood-2006-01-0329 · Cited by 511

See all 254

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.
ORCID: Koenen, Hans J. P. M.
Hilbrands, Luuk B.
Joosten, Irma
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
DOI: 10.1182/blood-2005-07-3032
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Rapamycin, and not cyclosporin A, preserves the highly suppressive CD27+ subset of human CD4+CD25+ regulatory T cells

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks