ArticleBlood2008
Differential impact of mammalian target of rapamycin inhibition on CD4+CD25+Foxp3+ regulatory T cells compared with conventional CD4+ T cells.
Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 227 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
227 citing papers in PubMed, 390 citations in OpenAlex.
- Everolimus-based immunosuppression induces alloreactive regulatory T cell expansion combined with loss of alloreactive effector T cells.Frontiers in immunology · 2026Trial
- A prospective single-center study on CNI-free GVHD prophylaxis with everolimus plus mycophenolate mofetil in allogeneic HCT.Annals of hematology · 2021Trial
- Trial
- Effect of Sirolimus on Immune Reconstitution Following Myeloablative Allogeneic Stem Cell Transplantation: An Ancillary Analysis of a Randomized Controlled Trial Comparing Tacrolimus/Sirolimus and Tacrolimus/Methotrexate (Blood and Marrow Transplant Clinical Trials Network/BMT CTN 0402).Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2019Trial
- A phase II/III randomized, multicenter trial of prednisone/sirolimusHaematologica · 2018Trial
- Bortezomib-based immunosuppression after reduced-intensity conditioning hematopoietic stem cell transplantation: randomized phase II results.Haematologica · 2018Trial
- Trial
- IL-2 promotes early Treg reconstitution after allogeneic hematopoietic cell transplantation.Haematologica · 2017Trial
- Trial
- Trial
- Everolimus for the treatment of uveitis refractory to cyclosporine A: a pilot study.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2013Trial
- A randomized phase II study to evaluate tacrolimus in combination with sirolimus or methotrexate after allogeneic hematopoietic cell transplantation.Haematologica · 2012Trial
- Comparison of short-term response and long-term outcomes after initial systemic treatment of chronic graft-versus-host disease.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2011Trial
- Isolation and expansion of human natural T regulatory cells for cellular therapy.Journal of immunological methods · 2010Trial
- Clinical development of tacrolimus-resistant regulatory T cells to enable simultaneous immunosuppression and immune regulation.Molecular therapy. Advances · 2026Article
- Inflame and restrain - the paradoxical roles of IL-12 and IL-23 in immunity.Nature reviews. Immunology · 2026Review
- Trackable Tolerogenic Macrophages Integrate PD-L1 and Rapamycin Signaling to Suppress Alloimmune Responses in Transplantation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Strategies for Evading Cellular Immunity Against Recombinant AAV Vectors in Gene Therapy.Current medical science · 2026Review
- Mechanisms of and mitigating strategies for cellular immune responses to CRISPR-associated nucleases in genome editing therapy.Frontiers in medicine · 2026Review
- CD38+ NK cells: novel players in immunoregulation.Frontiers in immunology · 2026Review
167 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
Based on their ability to control T-cell homeostasis, Foxp3(+)CD4(+)CD25(+) regulatory T cells (Tregs) are being considered for treatment of autoimmune disorders and acute graft-versus-host disease (aGVHD). When combining Tregs with the immunosuppressant rapamycin (RAPA), we observed reduced alloreactive conventional T-cell (Tconv) expansion and aGVHD lethality compared with each treatment alone. This synergistic in vivo protection was paralleled by intact expansion of polyclonal Tregs with conserved high FoxP3 expression. In contrast to Tconv, activation of Tregs with alloantigen and interleukin-2 preferentially led to signal transducer and activator of transcription 5 (STAT5) phosphorylation and not phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway activity. Expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a negative regulator of the PI3K/Akt/mTOR pathway, remained high in Tregs but not Tconv during stimulation. Conversely, targeted deletion of PTEN increased susceptibility of Tregs to mTOR inhibition by RAPA. Differential impact of RAPA as a result of reduced usage of the mTOR pathway in Tregs compared with conventional T cells explains the synergistic effect of RAPA and Tregs in aGVHD protection, which has important implications for clinical trials using Tregs.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.