Trial reportThe Journal of clinical investigation2014
IL-12-producing monocytes and HLA-E control HCMV-driven NKG2C+ NK cell expansion.
Trial report in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
What it found
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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
118 citing papers in PubMed, 186 citations in OpenAlex.
- Dynamic Changes in Natural Killer Cell Subset Frequencies in the Absence of Cytomegalovirus Infection.Frontiers in immunology · 2019Trial
- Natural killer cells against viral infection: from basic biology to immunotherapy.Precision clinical medicine · 2026Review
- HLA-E-Directed Accumulation of KIRInternational journal of molecular sciences · 2026Article
- The role of DAP12 in immune-related inflammatory diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Enhanced cytotoxicity of aging associated NKG2C + CD8 + T cells in ankylosing spondylitis via HLA-B27.Arthritis research & therapy · 2025Article
- Adaptive-like NK cell responses to influenza correlate with humoral immunity and are influenced by age and sex.bioRxiv : the preprint server for biology · 2025Article
- Yoda1, a Piezo1 agonist, induced latent HIV reactivation associated with upregulation of CD3/TCR complex and HLA genes.Research square · 2025Article
- Cytokine Production in Response to Soluble Leishmania Aethiopica Antigen by Whole Blood Cells from Patients with Different Clinical Presentations of Cutaneous Leishmaniasis.The American journal of tropical medicine and hygiene · 2025Article
- Persistence of a Skewed Repertoire of NK Cells in People with HIV-1 on Long-Term Antiretroviral Therapy.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Autologous T-Cell-Free Antigen Presentation System Unveils hCMV-Specific NK Cell Response.Cells · 2024Article
- Article
- Obtaining Gene-Modified HLA-E-Expressing Feeder Cells for Stimulation of Natural Killer Cells.Pharmaceutics · 2024Article
- Exploiting innate immunity for cancer immunotherapy.Molecular cancer · 2023Review
- Cardinal features of immune memory in innate lymphocytes.Nature immunology · 2023Review
- FcRγ- NK Cell Induction by Specific Cytomegalovirus and Expansion by Subclinical Viral Infections in Rhesus Macaques.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Advances in NK cell therapy for hematologic malignancies: NK source, persistence and tumor targeting.Blood reviews · 2023Review
- Streptococcus pneumoniae drives specific and lasting Natural Killer cell memory.PLoS pathogens · 2023Article
- The impact of HLA polymorphism on herpesvirus infection and disease.Immunogenetics · 2023Review
- Activating NKG2C Receptor: Functional Characteristics and Current Strategies in Clinical Applications.Archivum immunologiae et therapiae experimentalis · 2023Review
- Human natural killer cells: Form, function, and development.The Journal of allergy and clinical immunology · 2023Review
58 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human cytomegalovirus (HCMV) infection is the most common cause of congenital viral infections and a major source of morbidity and mortality after organ transplantation. NK cells are pivotal effector cells in the innate defense against CMV. Recently, hallmarks of adaptive responses, such as memory-like features, have been recognized in NK cells. HCMV infection elicits the expansion of an NK cell subset carrying an activating receptor heterodimer, comprising CD94 and NKG2C (CD94/NKG2C), a response that resembles the clonal expansion of adaptive immune cells. Here, we determined that expansion of this NKG2C(+) subset and general NK cell recovery rely on signals derived from CD14(+) monocytes. In a coculture system, a subset of CD14(+) cells with inflammatory monocyte features produced IL-12 in response to HCMV-infected fibroblasts, and neutralization of IL-12 in this model substantially reduced CD25 upregulation and NKG2C(+) subset expansion. Finally, blockade of CD94/NKG2C on NK cells or silencing of the cognate ligand HLA-E in infected fibroblasts greatly impaired expansion of NKG2C(+) NK cells. Together, our results reveal that IL-12, CD14(+) cells, and the CD94/NKG2C/HLA-E axis are critical for the expansion of NKG2C(+) NK cells in response to HCMV infection. Moreover, strategies targeting the NKG2C(+) NK cell subset have the potential to be exploited in NK cell-based intervention strategies against viral infections and cancer.
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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.