ArticleBlood2007
Direct inhibition of CD40L expression can contribute to the clinical efficacy of daclizumab independently of its effects on cell division and Th1/Th2 cytokine production.
Article in Blood, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- Daclizumab reduces CD25 levels on T cells through monocyte-mediated trogocytosis.Multiple sclerosis (Houndmills, Basingstoke, England) · 2014Trial
- IRF5 mediates adaptive immunity via altered glutamine metabolism, mTORC1 signaling and post-transcriptional regulation following T cell receptor activation.bioRxiv : the preprint server for biology · 2024Article
- A role for platelets in metabolic reprogramming of tumor-associated macrophages.Frontiers in physiology · 2023Review
- Elevated expression of activated TAnnals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · 2018Article
- Daclizumab: Development, Clinical Trials, and Practical Aspects of Use in Multiple Sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017Review
- Monoclonal antibodies in the treatment of multiple sclerosis: emergence of B-cell-targeted therapies.British journal of pharmacology · 2017Review
- Article
- CD154 blockade modulates the ratio of Treg to Th1 cells and prolongs the survival of allogeneic corneal grafts in mice.Experimental and therapeutic medicine · 2014Article
- Article
- Impaired NFAT and NFκB activation are involved in suppression of CD40 ligand expression by Δ(9)-tetrahydrocannabinol in human CD4(+) T cells.Toxicology and applied pharmacology · 2013Article
- Co-culture of the 55-6 B cell hybridoma with the EL-4 thymoma cell. Effect on cell growth and monoclonal antibody production.Cytotechnology · 2013Article
- Review
- What do effective treatments for multiple sclerosis tell us about the molecular mechanisms involved in pathogenesis?International journal of molecular sciences · 2012Review
- Article
- Long-term follow-up of patients with moderate aplastic anemia and pure red cell aplasia treated with daclizumab.Haematologica · 2010Article
- Long-term daclizumab therapy in relapsing-remitting multiple sclerosis.Therapeutic advances in neurological disorders · 2009Article
- CD28 and inducible costimulator (ICOS) signalling can sustain CD154 expression on activated T cells.Immunology · 2009Article
- Monoclonal antibody treatments for multiple sclerosis.Current treatment options in neurology · 2009Article
- Monoclonal antibody treatments for multiple sclerosis.Current neurology and neuroscience reports · 2008Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Humanized anti-CD25 antibodies (eg, daclizumab) have been successfully used to treat several autoimmune diseases. Paradoxically, IL-2 blockade in mice can induce autoimmunity. An interspecies difference in the relative contribution of IL-2 to CD25(+) T regulatory cell (CD25(+)Treg) versus CD25(+) effector cell function might explain this conundrum. Consistent with this are reports that daclizumab inhibits human CD25(+) effector cell cytokine production by blocking the expression of CD40L. However, in mice, IL-4 and IL-12 regulate CD40L expression. As human Th1/Th2 cytokine production is also dependent on IL-2, daclizumab's inhibition of CD40L expression could be due to an indirect, rather than a direct, effect of IL-2. Here, we clarify the mechanisms underlying CD40L expression. In contrast to the mouse, human CD40L is regulated by CD28 signaling and IL-2, not the principal Th1/Th2-polarizing cytokines. We find that CD40L is expressed on naive and memory cells and inhibited by daclizumab independently of cell division. Collectively, our results indicate that daclizumab could inhibit CD25(+) effector T-cell function in vivo by directly blocking CD40L expression. This difference between mice and human may help explain the paradoxical effects of IL-2R blockade in the 2 species.
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.