ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Functional NK cell repertoires are maintained through IL-2Rα and Fas ligand.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Trial
- Clonal selection of somatic mutations shapes NK cell memory.bioRxiv : the preprint server for biology · 2026Article
- A role for Fas/FasL-dependent NK-mediated cytotoxicity in infants with perinatal HIV.iScience · 2025Article
- New approaches of chimeric antigen receptor (CAR)-immune cell-based therapy in gastric cancer; highlight CAR-T and CAR-NK.Functional & integrative genomics · 2025Review
- The innate defenders: a review of natural killer cell immunotherapies in cancer.Frontiers in immunology · 2024Review
- Interleukin-15 enhanced the survival of human γδT cells by regulating the expression of Mcl-1 in neuroblastoma.Cell death discovery · 2022Article
- Increased Susceptibility of the CD57International journal of molecular sciences · 2021Article
- Article
- Efficient recruitment of c-FLIPCancer science · 2020Article
- NK cells are biologic and biochemical targets of 6-mercaptopurine in Crohn's disease patients.Clinical immunology (Orlando, Fla.) · 2017Article
- Natural Killer Cell Interactions with Classical and Non-Classical Human Leukocyte Antigen Class I in HIV-1 Infection.Frontiers in immunology · 2017Review
- A Two-Phase Expansion Protocol Combining Interleukin (IL)-15 and IL-21 Improves Natural Killer Cell Proliferation and Cytotoxicity against Rhabdomyosarcoma.Frontiers in immunology · 2017Article
- T Regulatory Cell Biology in Health and Disease.Current allergy and asthma reports · 2016Review
- Harnessing adaptive natural killer cells in cancer immunotherapy.Molecular oncology · 2015Review
- Newtonian cell interactions shape natural killer cell education.Immunological reviews · 2015Review
- Polyclonal Expansion of NKG2C(+) NK Cells in TAP-Deficient Patients.Frontiers in immunology · 2015Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Acquisition of a functional NK cell repertoire, known as education or licensing, is a complex process mediated through inhibitory receptors that recognize self. We found that NK cells containing self-killer Ig-like receptors for cognate HLA ligand in vivo were less susceptible to apoptosis. In vitro IL-15 withdrawal showed that uneducated NK cells upregulated Bim and Fas. Conversely, educated NK cells upregulated Fas ligand (FasL) under these conditions. Induction of cell death and Bim expression on uneducated cells correlated with increased IL-2Rα expression. Overexpression and knockdown studies showed that higher IL-2Rα limits NK cell survival in a novel manner that is independent from the role of IL-2 in activation-induced cell death. To study the role of FasL in induction of IL-2Rα(hi) NK cell death, a coculture assay with FasL-blocking Abs was used. IL-15 withdrawal led to FasL-dependent killing of IL-2Rα(hi) NK cells by more educated IL-2Rα(lo) NK cells. Finally, CMV reactivation induces a potent long-lasting population of licensed NK cells with enhanced survival. These findings show that education-dependent NK cell survival advantages and killing of uneducated NK cells result in the maintenance of a functional repertoire, which may be manipulated to exploit NK cells for cancer immunotherapy.
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