ArticleThe Journal of clinical investigation2024
Induced CD8α identifies human NK cells with enhanced proliferative fitness and modulates NK cell activation.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Clinical and Immunologic Effects of Extracorporeal Cytokine Removal in Patients with Septic Shock: A Randomized Controlled Trial.Shock (Augusta, Ga.) · 2026Trial
- Genome-wide association study and predictors of neonatal blood cell traits in Hispanic newborns.American journal of human genetics · 2026Article
- Safety and Feasibility of Infusing Ex Vivo Expanded Allogeneic Canine Natural Killer Cells for the Treatment of Metastatic Solid Tumours.Veterinary and comparative oncology · 2026Article
- RNF2 mediates H2A ubiquitination to promote colitis via suppressing monocyte-macrophage transition in mice.Nature communications · 2026Article
- Pediatric long COVID is characterized by myeloid CCR6 suppression and immune dysregulation.JCI insight · 2026Article
- Safety and Feasibility of InfusingbioRxiv : the preprint server for biology · 2026Article
- CD8α marks a Mycobacterium tuberculosis-reactive human NK cell population with high activation potential.Scientific reports · 2025Article
- Changes in circulating NK and innate-like T cells in type 1 and type 2 diabetes.Frontiers in immunology · 2025Article
- AI-assisted peripheral immune profiling reveals unconventional lymphocyte signatures associated with prognosis in soft tissue sarcoma patients.Frontiers in immunology · 2025Article
- CD8α and CD70 mark human natural killer cell populations which differ in cytotoxicity.Frontiers in immunology · 2025Article
- Striking a balance: the Goldilocks effect of CD8α expression on NK cells.The Journal of clinical investigation · 2024Article
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
The surface receptor CD8α is present on 20%-80% of human (but not mouse) NK cells, yet its function on NK cells remains poorly understood. CD8α expression on donor NK cells was associated with a lack of therapeutic responses in patients with leukemia in prior studies, thus, we hypothesized that CD8α may affect critical NK cell functions. Here, we discovered that CD8α- NK cells had improved control of leukemia in xenograft models compared with CD8α+ NK cells, likely due to an enhanced capacity for proliferation. Unexpectedly, we found that CD8α expression was induced on approximately 30% of previously CD8α- NK cells following IL-15 stimulation. These induced CD8α+ (iCD8α+) NK cells had the greatest proliferation, responses to IL-15 signaling, and metabolic activity compared with those that sustained existing CD8α expression (sustained CD8α+) or those that remained CD8α- (persistent CD8α-). These iCD8α+ cells originated from an IL-15Rβhi NK cell population, with CD8α expression dependent on the transcription factor RUNX3. Moreover, CD8A CRISPR/Cas9 deletion resulted in enhanced responses through the activating receptor NKp30, possibly by modulating KIR inhibitory function. Thus, CD8α status identified human NK cell capacity for IL-15-induced proliferation and metabolism in a time-dependent fashion, and its presence had a suppressive effect on NK cell-activating receptors.
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