ArticleBlood advances2020
IL-2 enhances ex vivo-expanded regulatory T-cell persistence after adoptive transfer.
Article in Blood advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 38 citations in OpenAlex.
- Double activation and low IL-2 manufacturing protocol increase expansion of healthy and patient-derived CAR-Tregs.Molecular therapy. Advances · 2026Article
- Cytokine-independent activation of STAT5 promotes the persistence and function of CD4Molecular therapy. Advances · 2026Article
- Harnessing Regulatory T Cells to Modulate Acute Brain Injury: From Mechanisms to Therapy.Molecular neurobiology · 2026Review
- Cellular Immunotherapies for Multiple Sclerosis: Mechanistic Insights and Clinical Advances.International journal of molecular sciences · 2026Review
- Regulatory T Cell-Based Adoptive Cell Therapy in Autoimmunity.International journal of molecular sciences · 2025Review
- Tetrahydrobiopterin enhances regulatory T- and mast cell proliferation and alters cytokines expression in a murine heart transplant model.Scientific reports · 2025Article
- Understanding Immune Dynamics in Liver Transplant Through Mathematical Modeling.Bulletin of mathematical biology · 2025Article
- Regulatory T cell therapy in lung transplantation: bridging the gap from bench to bedside.Frontiers in immunology · 2025Review
- IL-27/Blimp-1 axis regulates the differentiation and function of Tim-3+ Tregs during early pregnancy.JCI insight · 2024Article
- Role of FoxP3Human gene therapy · 2024Review
- Biomaterial-enhanced treg cell immunotherapy: A promising approach for transplant medicine and autoimmune disease treatment.Bioactive materials · 2024Review
- Augmenting regulatory T cells: new therapeutic strategy for rheumatoid arthritis.Frontiers in immunology · 2024Review
- Review
- Tumor-Infiltrating Lymphocytes and Adoptive Cell Therapy: State of the Art in Colorectal, Breast and Lung Cancer.Physiological research · 2023Review
- Real-world experience with low-dose IL-2 for children and young adults with refractory chronic graft-versus-host disease.Blood advances · 2023Article
- Article
- Precision sirolimus dosing in children: The potential for model-informed dosing and novel drug monitoring.Frontiers in pharmacology · 2023Review
- EWS::FLI1 and HOXD13 Control Tumor Cell Plasticity in Ewing Sarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Cell therapy in vascularized composite allotransplantation.Biomedical journal · 2022Review
- Trafficking and persistence of alloantigen-specific chimeric antigen receptor regulatory T cells in Cynomolgus macaque.Cell reports. Medicine · 2022Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
As regulatory T cell (Treg) adoptive therapy continues to develop clinically, there is a need to determine which immunomodulatory agents pair most compatibly with Tregs to enable persistence and stabilize suppressor function. Prior work has shown that mechanistic target of rapamycin inhibition can increase the stability of thymic Tregs. In this study, we investigated the transcriptomic signatures of ex vivo-expanded Tregs after adoptive transfer in the setting of clinically relevant immunosuppression using a nonhuman primate (NHP) model as a prelude to future transplant studies. Here, we found that adding interleukin-2 (IL-2) to rapamycin in vivo supported a logarithmic increase in the half-life of adoptively transferred carboxyfluorescein diacetate succinimidyl ester-labeled, autologous NHP Tregs, effectively doubling the number of cells in the peripheral blood Treg compartment compared with Treg infusion when rapamycin was given alone. Using single-cell transcriptomics, we found that transferred ex vivo-expanded Tregs initially exhibit a gene expression signature consistent with an activated state. Moreover, those cells with the highest levels of activation also expressed genes associated with p53-mediated apoptosis. In contrast, transferred Tregs interrogated at day +20 posttransfer demonstrated a gene signature more similar to published profiles of resting Tregs. Together, these preclinical data further support combining IL-2 and rapamycin in vivo as adjunctive therapy for ex vivo-expanded adoptively transferred Tregs and suggest that the activation status of ex vivo-expanded Tregs is critical to their persistence.
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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.