ArticleThe Journal of experimental medicine1999
Interleukin 2 receptor signaling regulates the perforin gene through signal transducer and activator of transcription (Stat)5 activation of two enhancers.
Article in The Journal of experimental medicine, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 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.
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Who cites it
46 citing papers in PubMed, 116 citations in OpenAlex.
- The immunological and clinical effects of mutated ras peptide vaccine in combination with IL-2, GM-CSF, or both in patients with solid tumors.Journal of translational medicine · 2014Trial
- Trial
- Cytotoxic CD4Signal transduction and targeted therapy · 2026Review
- Combining lenalidomide with IL-2 family of cytokines enhances activating receptor and perforin/granzyme expression in NK cells.PloS one · 2026Article
- Phenotypes, mechanisms, and therapeutic strategies of natural killer cell immunosenescence.Immunity & ageing : I & A · 2025Review
- Methylomes of human CD4 and CD8 memory T lymphocytes reveal tissue-specific epigenetic signatures for maintenance and recall function.Immunity & inflammation · 2025Article
- Perforin: An intriguing protein in allograft rejection immunology (Review).Experimental and therapeutic medicine · 2022Review
- Runx proteins and transcriptional mechanisms that govern memory CD8 T cell development.Immunological reviews · 2021Review
- CRISPR-Cas9-Edited Tacrolimus-Resistant Antiviral T Cells for Advanced Adoptive Immunotherapy in Transplant Recipients.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- HLA-G dimer targets Granzyme B pathway to prolong human renal allograft survival.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Fueling Cancer Immunotherapy With Common Gamma Chain Cytokines.Frontiers in immunology · 2019Review
- Ruxolitinib partially reverses functional natural killer cell deficiency in patients with signal transducer and activator of transcription 1 (STAT1) gain-of-function mutations.The Journal of allergy and clinical immunology · 2018Article
- Strategies to enhance NK cell function for the treatment of tumors and infections.Critical reviews in immunology · 2018Review
- Reduced PRF1 enhancer methylation in children with a history of severe RSV bronchiolitis in infancy: an association study.BMC pediatrics · 2017Article
- Selective Destruction of Interleukin 23-Induced Expansion of a Major Antigen-Specific γδ T-Cell Subset in Patients With Tuberculosis.The Journal of infectious diseases · 2017Article
- Promoting Immune Regulation in Type 1 Diabetes Using Low-Dose Interleukin-2.Current diabetes reports · 2016Review
- Cord blood PRF1 methylation patterns and risk of lower respiratory tract infections in infants: findings from the Ulm Birth Cohort.Medicine · 2015Article
- Article
- High-resolution nucleosome mapping of targeted regions using BAC-based enrichment.Nucleic acids research · 2013Article
- Acute psychosocial stress-mediated changes in the expression and methylation of perforin in chronic fatigue syndrome.Genetics & epigenetics · 2013Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Optimal T cell differentiation into effector cells with specialized functions requires the participation of cytokine receptor signals. In T helper cells, this process is controlled by chromatin changes and distal and proximal regulatory elements as well as specific transcription factors. Analogous events during cytotoxic T lymphocyte (CTL) differentiation remain to be identified. This process is known, however, to be crucially regulated by interleukin (IL)-2 receptor (R) signals. It is accompanied by the induction of perforin expression via a mechanism that does not entail proximal regulatory elements. In this report, transgenically expressed human perforin gene locus DNAs demonstrate that IL-2R signals target two IL-2-dependent enhancers approximately 15 and 1 kilobase upstream of the promoter. The most distal enhancer may also respond to TCR signals. In transient transfections, both enhancers required two identically spaced Stat-like elements for their activation, which was abolished by expression of a dominant negative signal transducer and activator of transcription (Stat)5 molecule, whereas a constitutively active Stat5 molecule bypassed the requirement for IL-2R signals. These results provide a molecular explanation for the activation of the perforin gene during CTL differentiation and complement the analysis of animals deficient in the activation of the IL-2R Stat signaling pathway by establishing perforin as a target gene.
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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.