Trial reportProceedings of the National Academy of Sciences of the United States of America2006
Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 288 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Double Blind Placebo-Controlled Phase I/II Clinical Trial of Idebenone in Patients With Primary Progressive Multiple Sclerosis
Investigating Mechanism of Action of DAC HYP in the Treatment of High-Inflammatory Multiple Sclerosis (MS)
Who cites it
288 citing papers in PubMed, 2 syntheses or guidelines pooled it, 590 citations in OpenAlex.
- Immunopathology of and potential therapeutics for secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome: a translational perspective.Experimental & molecular medicine · 2024Pooled it
- Daclizumab for relapsing remitting multiple sclerosis.The Cochrane database of systematic reviews · 2013Pooled it
- Sustained immunotolerance in multiple sclerosis after stem cell transplant.Annals of clinical and translational neurology · 2022Trial
- A CD8Nature communications · 2021Trial
- Repopulation of T, B, and NK cells following alemtuzumab treatment in relapsing-remitting multiple sclerosis.Journal of neuroinflammation · 2020Trial
- Adaptive Features of Natural Killer Cells in Multiple Sclerosis.Frontiers in immunology · 2019Trial
- Natural Killer Cells Regulate Th17 Cells After Autologous Hematopoietic Stem Cell Transplantation for Relapsing Remitting Multiple Sclerosis.Frontiers in immunology · 2018Trial
- Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial.PLoS medicine · 2016Trial
- Cutaneous Adverse Events in the Randomized, Double-Blind, Active-Comparator DECIDE Study of Daclizumab High-Yield Process Versus Intramuscular Interferon Beta-1a in Relapsing-Remitting Multiple Sclerosis.Advances in therapy · 2016Trial
- Blockade of the High-Affinity Interleukin-2 Receptors with Daclizumab High-Yield Process: Pharmacokinetic/Pharmacodynamic Analysis of Single- and Multiple-Dose Phase I Trials.Clinical pharmacokinetics · 2016Trial
- Natural killer cell subsets in cerebrospinal fluid of patients with multiple sclerosis.Clinical and experimental immunology · 2015Trial
- Safety, efficacy, and pharmacokinetics/pharmacodynamics of daclizumab (anti-CD25) in patients with adult T-cell leukemia/lymphoma.Clinical immunology (Orlando, Fla.) · 2014Trial
- Population pharmacokinetics of daclizumab high-yield process in healthy volunteers: integrated analysis of intravenous and subcutaneous, single- and multiple-dose administration.Clinical pharmacokinetics · 2014Trial
- Daclizumab reduces CD25 levels on T cells through monocyte-mediated trogocytosis.Multiple sclerosis (Houndmills, Basingstoke, England) · 2014Trial
- Effect of daclizumab high-yield process in patients with highly active relapsing-remitting multiple sclerosis.Journal of neurology · 2014Trial
- Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy.Journal of immunotherapy (Hagerstown, Md. : 1997) · 2013Trial
- CNS vasculitis in a patient with MS on daclizumab monotherapy.Neurology · 2013Trial
- Unconventional functions of natural killer cells in homeostasis and disease.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Taming immune responses to AAV gene therapy by programmed in vivo Treg expansion.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Host immune dysfunction and Mycoplasma pneumoniae immune evasion: dual drivers of pathogenesis in Mycoplasma pneumoniae pneumonia.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
228 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Administration of daclizumab, a humanized mAb directed against the IL-2Ralpha chain, strongly reduces brain inflammation in multiple sclerosis patients. Here we show that daclizumab treatment leads to only a mild functional blockade of CD4(+) T cells, the major candidate in multiple sclerosis pathogenesis. Instead, daclizumab therapy was associated with a gradual decline in circulating CD4(+) and CD8(+) T cells and significant expansion of CD56(bright) natural killer (NK) cells in vivo, and this effect correlated highly with the treatment response. In vitro studies showed that NK cells inhibited T cell survival in activated peripheral blood mononuclear cell cultures by a contact-dependent mechanism. Positive correlations between expansion of CD56(bright) NK cells and contraction of CD4(+) and CD8(+) T cell numbers in individual patients in vivo provides supporting evidence for NK cell-mediated negative immunoregulation of activated T cells during daclizumab therapy. Our data support the existence of an immunoregulatory pathway wherein activated CD56(bright) NK cells inhibit T cell survival. This immunoregulation has potential importance for the treatment of autoimmune diseases and transplant rejection and toward modification of tumor immunity.
Indexed as
Identifiers
What OpenQuestion holds
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.