ArticleJournal of immunology (Baltimore, Md. : 1950)2015
NK Cell Proliferation Induced by IL-15 Transpresentation Is Negatively Regulated by Inhibitory Receptors.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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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
18 citing papers in PubMed, 29 citations in OpenAlex.
- Immunology of Normal Pregnancy and Preeclampsia and the Role of Placental Non-Classical HLA and Decidual NK Cells.International journal of molecular sciences · 2026Review
- Adipocyte-derived LTB4 programs human NKG2AJournal for immunotherapy of cancer · 2026Article
- A human tumor-immune organoid model of glioblastoma.Cell reports · 2026Article
- A Human Tumor-Immune Organoid Model of Glioblastoma.bioRxiv : the preprint server for biology · 2025Article
- The mechanisms underlying alcohol-induced decreased splenic size: A network meta-analysis study.Alcohol, clinical & experimental research · 2024Article
- The NK cell checkpoint NKG2A maintains expansion capacity of human NK cells.Scientific reports · 2023Article
- The role of GATA2 in adult hematopoiesis and cell fate determination.Frontiers in cell and developmental biology · 2023Review
- Diminished cell proliferation promotes natural killer cell adaptive-like phenotype by limiting FcεRIγ expression.The Journal of experimental medicine · 2022Article
- IL-15Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Clinically applicable CD34Cancer immunology, immunotherapy : CII · 2021Article
- Transcription Factors Associated With IL-15 Cytokine Signaling During NK Cell Development.Frontiers in immunology · 2021Review
- Analysis of Human Natural Killer Cell Metabolism.Journal of visualized experiments : JoVE · 2020Article
- Article
- In the absence of natural killer cell activation donor-specific antibody mediates chronic, but not acute, kidney allograft rejection.Kidney international · 2019Article
- Remodeling of secretory lysosomes during education tunes functional potential in NK cells.Nature communications · 2019Article
- Dendritic Cell-Derived IL-32α: A Novel Inhibitory Cytokine of NK Cell Function.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Independent control of natural killer cell responsiveness and homeostasis at steady-state by CD11c+ dendritic cells.Scientific reports · 2016Article
- Impaired NK-mediated regulation of T-cell activity in multiple sclerosis is reconstituted by IL-2 receptor modulation.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
IL-15 bound to the IL-15Rα-chain (IL-15Rα) is presented in trans to cells bearing the IL-2Rβ-chain and common γ-chain. As IL-15 transpresentation occurs in the context of cell-to-cell contacts, it has the potential for regulation by and of other receptor-ligand interactions. In this study, human NK cells were tested for the sensitivity of IL-15 transpresentation to inhibitory receptors. Human cells expressing HLA class I ligands for inhibitory receptors KIR2DL1, KIR2DL2/3, or CD94-NKG2A were transfected with IL-15Rα. Proliferation of primary NK cells in response to transpresented IL-15 was reduced by engagement of either KIR2DL1 or KIR2DL2/3 by cognate HLA-C ligands. Inhibitory KIR-HLA-C interactions did not reduce the proliferation induced by soluble IL-15. Therefore, transpresentation of IL-15 is subject to downregulation by MHC class I-specific inhibitory receptors. Similarly, proliferation of the NKG2A(+) cell line NKL induced by IL-15 transpresentation was inhibited by HLA-E. Coengagement of inhibitory receptors, either KIR2DL1 or CD94-NKG2A, did not inhibit phosphorylation of Stat5 but inhibited selectively phosphorylation of Akt and S6 ribosomal protein. IL-15Rα was not excluded from, but was evenly distributed across, inhibitory synapses. These findings demonstrate a novel mechanism to attenuate IL-15-dependent NK cell proliferation and suggest that inhibitory NK cell receptors contribute to NK cell homeostasis.
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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.