ArticleJournal of the American Society of Nephrology : JASN2015
Central Role of CD45RA- Foxp3hi Memory Regulatory T Cells in Clinical Kidney Transplantation Tolerance.
Article in Journal of the American Society of Nephrology : JASN, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
60 citing papers in PubMed, 2 syntheses or guidelines pooled it, 110 citations in OpenAlex.
- The applications of DNA methylation as a biomarker in kidney transplantation: a systematic review.Clinical epigenetics · 2022Pooled it
- Regulatory cell therapy in kidney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials.Lancet (London, England) · 2020Pooled it
- Immunophenotypic Profiling of Lymphocyte Subsets in Children and Adolescents With Acute Lymphoblastic Leukaemia: Immune Dysregulation Before and After Remission.Journal of immunology research · 2026Article
- Cellular Immunity in Chronic Kidney Disease and Changes After Kidney Transplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2026Article
- CD25Frontiers in immunology · 2026Article
- Chimerism and immunological tolerance in solid organ transplantation.Seminars in immunopathology · 2025Review
- Purinoreceptor P2X7 in Extracellular ATP-Mediated Inflammation through the Spectrum of Kidney Diseases and Kidney Transplantation.Journal of the American Society of Nephrology : JASN · 2025Review
- Evaluating Activated Regulatory T Cells as a Biomarker of Chronic Allograft Inflammation in Pediatric Kidney Transplant Recipients.Pediatric transplantation · 2025Article
- Targeting T helper 17 cells: emerging strategies for overcoming transplant rejection.Clinical transplantation and research · 2024Review
- Rise of a CD27European journal of immunology · 2024Article
- The balance between memory and regulatory cell populations in kidney transplant recipients with operational tolerance.Clinical and experimental immunology · 2024Article
- Regulatory T cells in autoimmune kidney diseases and transplantation.Nature reviews. Nephrology · 2023Review
- High-dimensional profiling of pediatric immune responses to solid organ transplantation.Cell reports. Medicine · 2023Article
- Kidney allograft rejection is associated with an imbalance of B cells, regulatory T cells and differentiated CD28-CD8+ T cells: analysis of a cohort of 1095 graft biopsies.Frontiers in immunology · 2023Article
- Revisiting transplant immunology through the lens of single-cell technologies.Seminars in immunopathology · 2023Review
- Memory regulatory T cells in pregnancy.Frontiers in immunology · 2023Review
- Burnstock oration - purinergic signalling in kidney transplantation.Purinergic signalling · 2022Review
- Forced Fox-P3 expression can improve the safety and antigen-specific function of engineered regulatory T cells.Journal of autoimmunity · 2022Article
- Biomarkers of immune tolerance in kidney transplantation: an overview.Pediatric nephrology (Berlin, Germany) · 2022Review
- The Association between Regulatory T Cell Subpopulations and Severe Pneumonia Post Renal Transplantation.Journal of immunology research · 2022Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of Foxp3(+) regulatory T cells (Tregs) in operational tolerance remains elusive, as initial results revealed an increased frequency of this subset in tolerant patients but no functional differences compared with immunosuppressed recipients. In addition, recent studies of regulatory B cells strongly suggest that Tregs may not have a central role in kidney transplantation tolerance. However, recent investigations of the crucial role of Foxp3 demethylation in Treg function and the possibility of identifying distinct Foxp3 T cell subsets prompted us to more thoroughly characterize Tregs in operationally tolerant patients. Thus, we studied the level of demethylation of the Foxp3 Treg-specific demethylated region (TSDR) in circulating CD4(+) T cells and analyzed Treg subset frequency in tolerant patients, healthy volunteers, patients with stable graft function under immunosuppression, and chronically rejecting recipients. We observed a higher proportion of CD4(+) T cells with demethylated Foxp3 and a specific expansion of CD4(+) CD45RA(-) Foxp3(hi) memory Tregs exclusively in tolerant patients. The memory Tregs of tolerant recipients exhibited increased Foxp3 TSDR demethylation, expressed higher levels of CD39 and glucocorticoid-induced TNF-related receptor, and harbored greater suppressive properties than memory Tregs from patients with stable graft function. Taken together, our data demonstrate that operationally tolerant patients mobilize an array of potentially suppressive cells, including not only regulatory B cells but also Tregs. Our results also indicate that tolerant patients have potent CD4(+)CD45RA(-) Foxp3(hi) memory Tregs with a specific Foxp3 TSDR demethylation pattern, which may contribute to the maintenance of graft tolerance.
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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.