ArticleTransplantation2010
A novel clinically relevant approach to tip the balance toward regulation in stringent transplant model.
Article in Transplantation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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
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Who cites it
19 citing papers in PubMed, 42 citations in OpenAlex.
- Regulatory T cell homeostasis: Requisite signals and implications for clinical development of biologics.Clinical immunology (Orlando, Fla.) · 2023Review
- Autophagy-lysosome inhibitor chloroquine prevents CTLA-4 degradation of T cells and attenuates acute rejection in murine skin and heart transplantation.Theranostics · 2020Article
- Role of Memory T Cells in Allograft Rejection and Tolerance.Frontiers in immunology · 2017Review
- Impact of Immune-Modulatory Drugs on Regulatory T Cell.Transplantation · 2016Review
- CD4 T Cell Help via B Cells Is Required for Lymphopenia-Induced CD8 T Cell Proliferation.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Differential sensitivity of regulatory and effector T cells to cell death: a prerequisite for transplant tolerance.Frontiers in immunology · 2015Review
- Regulatory T cells as immunotherapy.Frontiers in immunology · 2014Review
- Attenuation of donor-reactive T cells allows effective control of allograft rejection using regulatory T cell therapy.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2014Article
- Pretransplant antithymocyte globulin has increased efficacy in controlling donor-reactive memory T cells in mice.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2013Article
- Prolonged, low-dose anti-thymocyte globulin, combined with CTLA4-Ig, promotes engraftment in a stringent transplant model.PloS one · 2013Article
- Context and location dependence of adaptive Foxp3(+) regulatory T cell formation during immunopathological conditions.Cellular immunology · 2012Review
- BIOMARKERS OF OPERATIONAL TOLERANCE IN SOLID ORGAN TRANSPLANTATION.Expert opinion on medical diagnostics · 2012Article
- Ex vivo expansion of human Tregs by rabbit ATG is dependent on intact STAT3-signaling in CD4⁺ T cells and requires the presence of monocytes.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2012Article
- CD4(+)Foxp3(+) regulatory T cell therapy in transplantation.Journal of molecular cell biology · 2012Review
- Rejection and regulation: a tight balance.Current opinion in organ transplantation · 2012Review
- Translating tolerogenic therapies to the clinic - where do we stand?Frontiers in immunology · 2012Article
- T-cell co-stimulatory blockade in kidney transplantation: back to the bench.Kidney international supplements · 2011Article
- Paradoxical aspects of rapamycin immunobiology in transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2011Review
- TIM-3: a novel regulatory molecule of alloimmune activation.Journal of immunology (Baltimore, Md. : 1950) · 2010Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundRegulatory T cells (Tregs) actively regulate alloimmune responses and promote transplantation tolerance. Thymoglobulin, a rabbit polyclonal antithymocyte globulin (ATG), is a widely used induction therapy in clinical organ transplantation that depletes peripheral T cells. However, resistance to tolerance induction is seen with certain T-cell depleting strategies and is attributed to alterations in the balance of naive, memory and Tregs. The exact mechanism of action of ATG and its effects on the homeostasis and balance between Tregs and T-effector-memory cells (Tem) are unknown.
methodsA novel antibody reagent, rabbit polyclonal anti-murine thymocyte globulin (mATG), generated by the same process used to manufacture thymoglobulin, was used alone or in combination with CTLA4Ig or sirolimus (SRL) in a stringent fully major histocompatibility complex-mismatched murine skin allograft model to study graft survival and mechanisms involved.
resultsmATG depletes T cells but preferentially spares CD25+ natural Tregs which limit skewing of T-cell repertoire toward Tem phenotype among the recovering T cells. T-cell depletion with mATG combined with CTLA4Ig and SRL synergize to prolong graft survival by tipping the Treg/Tem balance further in favor of Tregs by preserving Tregs, facilitating generation of new Tregs by a conversion mechanism and limiting Tem expansion in response to alloantigen and homeostatic proliferation.
conclusionsSimultaneous T-cell depletion with ATG and costimulatory blockade, combined with SRL, synergizes to promote regulation and prolong allograft survival in a stringent transplant model. These results provide the rationale for translating such novel combination therapy to promote regulation in primate and human organ transplantation.
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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.