ArticleProceedings of the National Academy of Sciences of the United States of America2010
Mature natural killer cells with phenotypic and functional alterations accumulate upon sustained stimulation with IL-15/IL-15Ralpha complexes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed.
- Multi-Dimensional Flow Cytometry Analyses Reveal a Dichotomous Role for Nitric Oxide in Melanoma Patients Receiving Immunotherapy.Frontiers in immunology · 2020Trial
- The CREM-IL-15 axis: decoding the persistence-exhaustion paradox in NK cell immunotherapy.Cancer immunology, immunotherapy : CII · 2026Review
- PEG-RLI: A Long-Acting IL-15 Agonist That Produces Massive Levels of CD8Pharmaceutics · 2026Article
- Constitutive RLI Armoring Enhances CAR-NK Cell Effector Functions but Causes Lethal Toxicity In Vivo.International journal of molecular sciences · 2026Article
- Advances in IL-15-Based Cancer Immunotherapy and Divergent Immunological Effects of IL-2 and IL-15 Signaling via the Shared IL-2Rβγ Receptor.Frontiers in immunology · 2026Review
- Splenic TNF-α signaling potentiates the innate-to-adaptive transition of antiviral NK cells.Immunity · 2025Article
- Nanrilkefusp alfa (SOT101), an IL-15 receptor βγ superagonist, as a single agent or with anti-PD-1 in patients with advanced cancers.Cell reports. Medicine · 2025Article
- Regulation of NK cell development, maturation, and antitumor responses by the nuclear receptor NR2F6.Cell death & disease · 2025Article
- CD8α and CD70 mark human natural killer cell populations which differ in cytotoxicity.Frontiers in immunology · 2025Article
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- No time to die: Epigenetic regulation of natural killer cell survival.Immunological reviews · 2024Review
- Interferon-epsilon is a novel regulator of NK cell responses in the uterus.EMBO molecular medicine · 2024Article
- A structural, genetic and clinical comparison of CAR-T cells and CAR-NK cells: companions or competitors?Frontiers in immunology · 2024Review
- Single-cell profiling aligns CD56Frontiers in immunology · 2024Article
- Article
- In Vivo Zymosan Treatment Induces IL15-Secreting Macrophages and KLRG1-Expressing NK Cells in Mice.Molecules (Basel, Switzerland) · 2023Article
- Article
- The roles of different forms of IL-15 in human melanoma progression.Frontiers in immunology · 2023Article
- Harnessing IL-15 signaling to potentiate NK cell-mediated cancer immunotherapy.Trends in immunology · 2022Review
- Enhanced development of functional human NK cells in NOD-scid-IL2rgFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
23 more citing papers are in PubMed but not listed here.
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5 authors.
Funding
Abstract
Cytotoxic lymphocytes such as natural killer (NK) and CD8 T cells play important roles in immunosurveillance by killing virally infected or malignant cells. The homeostatic cytokine, IL-15, promotes the development, function, and survival of NK and CD8 T cells. IL-15 is normally presented in trans as a surface complex with IL-15 receptor-alpha-chain (IL-15Rα) by dendritic cells (DCs) and monocytes. Signaling by IL-15 occurs via the IL-2/IL-15 receptor β-chain (CD122) which is expressed primarily by NK1.1(+) cells and CD8 T cells. The use of preformed complexes of IL-15 with soluble IL-15Rα complexes to boost the effector function of CD122(+) cytolytic lymphocytes such as NK and CD8 T cells has recently gained considerable attention. Here we describe the impact of transient and prolonged in vivo stimulation by IL-15/IL-15Rα complexes on NK and CD8 T cells. Whereas transitory stimulation increased the number of activated NK cells and significantly enhanced their effector function, prolonged stimulation by IL-15/IL-15Rα complexes led to a marked accumulation of mature NK cells with considerably impaired activation, cytotoxicity, and proliferative activity, and an altered balance of activating and inhibitory receptors. In contrast to NK cells, CD8 T cells exhibited an activated phenotype and robust T cell receptor stimulation and effector function upon chronic stimulation with IL-15/IL-15Rα complexes. Thus, prolonged stimulation with the strong activating signal leads to a preferential accrual of mature NK cells with altered activation and diminished functional capacity. These findings point to a negative feedback mechanism to preferentially counterbalance excessive NK cell activity and may have important implications for cytokine immunotherapy.
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