ArticlePloS one2014
Inhibition of calcineurin abrogates while inhibition of mTOR promotes regulatory T cell expansion and graft-versus-host disease protection by IL-2 in allogeneic bone marrow transplantation.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 37 citations in OpenAlex.
- Regulatory T cell therapies: biological foundations, engineering strategies, and clinical translation.Frontiers in immunology · 2026Review
- Graft-Versus-Host Disease Mouse Models: A Clinical-Translational Perspective.Methods in molecular biology (Clifton, N.J.) · 2025Review
- The role of macrophages in the mitigation by decitabine of acute allograft rejection.Frontiers in transplantation · 2025Article
- Hypomethylating therapy mitigates acute allograft rejection in a murine lung transplant model.Frontiers in transplantation · 2025Article
- Concomitant use of interleukin-2 and tacrolimus suppresses follicular helper T cell proportion and exerts therapeutic effect against lupus nephritis in systemic lupus erythematosus-like chronic graft versus host disease.Frontiers in immunology · 2024Article
- Hematopoietic stem cell-derived Tregs are essential for maintaining favorable B cell lymphopoiesis following posttransplant cyclophosphamide.JCI insight · 2023Article
- An Overview of Autophagy in Hematopoietic Stem Cell Transplantation.Frontiers in bioengineering and biotechnology · 2022Review
- The Effectiveness of Ruxolitinib for Acute/Chronic Graft-versus-Host Disease in Children: A Retrospective Study.Drug design, development and therapy · 2021Article
- The Pursuit of Regulatory T Cells in the Induction of Transplant Tolerance.Advances in experimental medicine and biology · 2021Article
- Rapamycin-based graft-versus-host disease prophylaxis increases the immunosuppressivity of myeloid-derived suppressor cells without affecting T cells and anti-tumor cytotoxicity.Clinical and experimental immunology · 2020Article
- Transient antibody targeting of CD45RC inhibits the development of graft-versus-host disease.Blood advances · 2020Article
- Development of ImmTOR Tolerogenic Nanoparticles for the Mitigation of Anti-drug Antibodies.Frontiers in immunology · 2020Review
- Genetic disruption ofAmerican journal of physiology. Renal physiology · 2019Article
- MiR-548a-3p Promotes Keratinocyte Proliferation Targeting PPP3R1 after Being Induced by IL-22.Inflammation · 2018Article
- Low-dose interleukin-2 as a modulator of Treg homeostasis after HSCT: current understanding and future perspectives.International journal of hematology · 2018Review
- T-Cell Metabolism in Hematopoietic Cell Transplantation.Frontiers in immunology · 2018Review
- Article
- A New Immunosuppressive Molecule Emodin Induces both CD4Frontiers in immunology · 2017Article
- Pharmacologic targeting of regulatory T cells for solid organ transplantation: current and future prospects.Drugs · 2015Review
- The calcineurin-NFAT axis controls allograft immunity in myeloid-derived suppressor cells through reprogramming T cell differentiation.Molecular and cellular biology · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Regulatory T cells (Treg)s attenuate excessive immune responses, making their expansion beneficial in immune-mediated diseases including allogeneic bone marrow transplantation (BMT)-associated graft-versus-host disease (GVHD). We have recently reported that Treg expansion does not require phospholipase Cγ activation when IL-2 is provided. As such, the combination of IL-2 and a calcineurin inhibitor (Cyclosporine A; CsA) expands Tregs while inhibiting Tconv proliferation and protects against a mouse model of multiple sclerosis. However, CsA inhibits Treg proliferation in the presence of a TCR stimulus, suggesting that CsA may negatively impact Treg proliferation when they receive strong allogeneic MHC-mediated TCR signals. In this study, we show that CsA inhibits Treg proliferation and inducible Treg generation in allogeneic but not in syngeneic BMT when IL-2 is provided. In contrast to CsA, the mTOR inhibitor (Rapamycin) almost completely suppressed IL-2-mediated Treg proliferation. However, CsA and Rapamycin inhibited Treg proliferation to a similar extent when TCR stimulation was provided. Furthermore, Rapamycin promoted Treg expansion and inducible Treg generation in allogeneic BMT recipients treated with IL-2. Consistent with these observations, CsA abrogated while Rapamycin promoted the protective effect of IL-2 on allogeneic BMT-induced GVHD. These results suggest that while CsA permits IL-2-induced Treg proliferation in the syngeneic setting (absence of strong TCR signals), CsA in combination with IL-2 may be detrimental for Treg proliferation in an allogeneic setting. Thus, in allogeneic settings, an mTOR inhibitor such as Rapamycin is a better choice for adjunct therapy with IL-2 in expansion of Tregs and protection against allogeneic BMT-induced GVHD.
Indexed as
Identifiers
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.