ArticleTransplantation2009
The human "Treg MLR": immune monitoring for FOXP3+ T regulatory cell generation.
Article in Transplantation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Dawn of Monitoring Regulatory T Cells in (Pre-)clinical Studies: Their Relevance Is Slowly Recognised.Frontiers in medicine · 2020Pooled it
- Systemic immunoregulatory and proteogenomic effects of tacrolimus to sirolimus conversion in liver transplant recipients.Hepatology (Baltimore, Md.) · 2013Trial
- Article
- Challenges with sirolimus experimental data to inform QSP model of post-transplantation cyclophosphamide regimens.Clinical and translational science · 2024Review
- LAG-3xPD-L1 bispecific antibody potentiates antitumor responses of T cells through dendritic cell activation.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Heparin affects the induction of regulatory T cells independent of anti-coagulant activity and suppresses allogeneic immune responses.Clinical and experimental immunology · 2020Article
- Delivery of Rapamycin Using In Situ Forming Implants Promotes Immunoregulation and Vascularized Composite Allograft Survival.Scientific reports · 2019Article
- A Phase I Clinical Trial with Ex Vivo Expanded Recipient Regulatory T cells in Living Donor Kidney Transplants.Scientific reports · 2018Article
- Updated follow-up of a tolerance protocol in HLA-identical renal transplant pairs given donor hematopoietic stem cells.Human immunology · 2018Review
- Generation and Characterization of Alloantigen-Specific Regulatory T Cells For Clinical Transplant Tolerance.Scientific reports · 2018Article
- Induction of a Regulatory Phenotype in CD3+ CD4+ HLA-DR+ T Cells after Allogeneic Mixed Lymphocyte Culture; Indications of Both Contact-Dependent and -Independent Activation.International journal of molecular sciences · 2017Article
- Low incidence of acute rejection in hepatitis B virus positive liver transplant recipients and the impact of hepatitis B immunoglobulin.Human immunology · 2016Article
- Nonchimeric HLA-Identical Renal Transplant Tolerance: Regulatory Immunophenotypic/Genomic Biomarkers.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2016Article
- Article
- Towards programming immune tolerance through geometric manipulation of phosphatidylserine.Biomaterials · 2015Article
- Inhibitory effects of belatacept on allospecific regulatory T-cell generation in humans.Transplantation · 2013Article
- Cord-blood-derived mesenchymal stromal cells downmodulate CD4+ T-cell activation by inducing IL-10-producing Th1 cells.Stem cells and development · 2013Article
- Evolving approaches of hematopoietic stem cell-based therapies to induce tolerance to organ transplants: the long road to tolerance.Clinical pharmacology and therapeutics · 2013Review
- Immune responses against islet allografts during tapering of immunosuppression--a pilot study in 5 subjects.Clinical and experimental immunology · 2012Article
- Favorable effects of alemtuzumab on allospecific regulatory T-cell generation.Human immunology · 2012Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundControversy exists about the conditions effecting the development of forkhead/winghead helix transcription factor P3 (FOXP3) expressing T cells and their relevance in transplant recipients.
methodsWe generated carboxy-fluorescein diacetate succinimidyl ester-labeled CD4+CD25 high FOXP3+ cells in mixed lymphocyte reactions (MLRs) ("the Treg MLR"), with varying human leukocyte antigen (HLA) disparities and cell components. Five color flow cytometry and H-thymidine uptakes were the readouts.
results(1) Despite lower stimulation indices (SIs) than two DR-mismatched MLRs, 2 DR-matched MLRs generated more than twofold higher percentages when gating on proliferating CD4+CD25 high FOXP3+ cells; (2) Even with low numbers of proliferating cells, autologous and HLA identical MLRs generated the highest FOXP3+:FOXP3- cell ratios; (3) Elimination of either non-CD3+ responding cells (resulting in "direct presentation" only) or responding CD25+ (Treg generating) cells increased the SI but inhibited proliferating CD4+CD25 high FOXP3+ cell development; (4) MLR-generated CD4+CD25 high FOXP3+ cells added as third components specifically inhibited the same freshly set MLR SI and caused recruitment of new CD4+CD25 high FOXP3+ cells. As an example of the "Treg MLR" immune monitoring potential, addition of third component peripheral blood mononuclear cell containing high percentages of CD4+CD25 high FOXP3+ cells from an HLA identical kidney transplant recipient (in a tolerance protocol) caused donor-specific Treg MLR inhibition or recruitment. This was similar to the third component MLR Tregs generated entirely in vitro.
conclusionIn the Treg MLR, the generation of CD4+CD25 high FOXP3+ cells is more pronounced in the context of self-recognition (HLA matching, indirect presentation). These cells can be assayed for MLR inhibitory and Treg recruitment functions, so as to immunologically monitor the allospecific regulation after transplantation.
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Registered trials
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