Trial reportImmunology2013
Interleukin-21 (IL-21) synergizes with IL-2 to enhance T-cell receptor-induced human T-cell proliferation and counteracts IL-2/transforming growth factor-β-induced regulatory T-cell development.
Trial report in Immunology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
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
29 citing papers in PubMed, 48 citations in OpenAlex.
- Adaptive-like CAR-iPSC-CD4⁺ T cells outperform CD8⁺ counterparts in sustained ALL control.Inflammation and regeneration · 2026Article
- Nrf2 drives activation-driven expansion of CD4Cell reports · 2025Article
- Therapeutic targeting of TGF-β in lung cancer.The FEBS journal · 2025Review
- γδT cells, a key subset of T cell for cancer immunotherapy.Frontiers in immunology · 2025Review
- TGF-β: an active participant in the immune and metabolic microenvironment of multiple myeloma : TGF-β in the microenvironment of multiple myeloma.Annals of hematology · 2024Review
- IL-2 family cytokines IL-9 and IL-21 differentially regulate innate and adaptive type 2 immunity in asthma.The Journal of allergy and clinical immunology · 2024Article
- Establishment of a protocol for rapidly expanding Epstein-Barr-virus-specific cytotoxic T cells with enhanced cytotoxicity.BMC cancer · 2024Article
- Pro-inflammatory cytokine IL-21 correlates with the reactive oxygen species and 25-hydroxy vitamin D in rheumatoid arthritis patients.Immunity, inflammation and disease · 2024Article
- TCR-engaging scaffolds selectively expand antigen-specific T-cells with a favorable phenotype for adoptive cell therapy.Journal for immunotherapy of cancer · 2023Article
- Transcriptional determinants of cancer immunotherapy response and resistance.Trends in cancer · 2022Review
- Targeting TGF-β signaling in the multiple myeloma microenvironment: Steering CARs and T cells in the right direction.Frontiers in cell and developmental biology · 2022Review
- Lactobacillus plantarum surface-displayed ASFV (p54) with porcine IL-21 generally stimulates protective immune responses in mice.AMB Express · 2021Article
- Interleukin-21 (IL-21) Downregulates Dendritic Cell Cytokine Responses to Helicobacter pylori and Modulates T Lymphocyte IL-17A Expression in Peyer's Patches during Infection.Infection and immunity · 2019Article
- Interleukin-2 induces extracellular matrix synthesis and TGF-β2 expression in retinal pigment epithelial cells.Development, growth & differentiation · 2019Article
- Review
- Interleukin (IL)-21 in Inflammation and Immunity During Parasitic Diseases.Frontiers in cellular and infection microbiology · 2019Review
- On-demand serum-free media formulations for human hematopoietic cell expansion using a high dimensional search algorithm.Communications biology · 2019Article
- Antigen-specific CD8+ memory stem T cells generated from human peripheral blood effectively eradicate allogeneic targets in mice.Stem cell research & therapy · 2018Article
- Pharmacokinetic properties of radiolabeled mutant Interleukin-2v: a PET imaging study.Oncotarget · 2018Article
- Obesity altered T cell metabolism and the response to infection.Current opinion in immunology · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin-2 (IL-2) is a mainstay for current immunotherapeutic protocols but its usefulness in patients is reduced by severe toxicities and because IL-2 facilitates regulatory T (Treg) cell development. IL-21 is a type I cytokine acting as a potent T-cell co-mitogen but less efficient than IL-2 in sustaining T-cell proliferation. Using various in vitro models for T-cell receptor (TCR)-dependent human T-cell proliferation, we found that IL-21 synergized with IL-2 to make CD4(+) and CD8(+) T cells attain a level of expansion that was impossible to obtain with IL-2 alone. Synergy was mostly evident in naive CD4(+) cells. IL-2 and tumour-released transforming growth factor-β (TGF-β) are the main environmental cues that cooperate in Treg cell induction in tumour patients. Interleukin-21 hampered Treg cell expansion induced by IL-2/TGF-β combination in naive CD4(+) cells by facilitating non-Treg over Treg cell proliferation from the early phases of cell activation. Conversely, IL-21 did not modulate the conversion of naive activated CD4(+) cells into Treg cells in the absence of cell division. Treg cell reduction was related to persistent activation of Stat3, a negative regulator of Treg cells associated with down-modulation of IL-2/TGF-β-induced phosphorylation of Smad2/3, a positive regulator of Treg cells. In contrast to previous studies, IL-21 was completely ineffective in counteracting the suppressive activity of Treg cells on naive and memory, CD4(+) and CD8(+) T cells. Present data provide proof-of-concept for evaluating a combinatorial approach that would reduce the IL-2 needed to sustain T-cell proliferation efficiently, thereby reducing toxicity and controlling a tolerizing mechanism responsible for the contraction of the T-cell response.
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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.