ArticleThe Journal of biological chemistry2010
Homotypic cell to cell cross-talk among human natural killer cells reveals differential and overlapping roles of 2B4 and CD2.
Article in The Journal of biological chemistry, 2010. 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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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Could the Immune Modulation of Invariant Natural Killer T Cell and the Expression of CD244 and CD196 on Natural Killer Cell Subtypes Impact the Treatment Outcomes of Acute Myeloid Leukemia Patients?Journal of hematology · 2026Article
- 2B4/CD244 Signaling in Immune Regulation and Its Role in Infection, Cancer, and Immune Tolerance.ImmunoTargets and therapy · 2025Review
- Exploring the genetic factors behind the discrepancy in resistance to bovine tuberculosis between African zebu cattle and European taurine cattle.Scientific reports · 2024Article
- Networked Cluster Formation via Trigonal Lipid Modules for Augmented Ex Vivo NK Cell Priming.International journal of molecular sciences · 2024Article
- SLAM-family receptors come of age as a potential molecular target in cancer immunotherapy.Frontiers in immunology · 2023Review
- Distinct Signatures in the Receptor Repertoire Discriminate CD56bright and CD56dim Natural Killer Cells.Frontiers in immunology · 2020Article
- Semaphorin 7A modulates cytokine-induced memory-like responses by human natural killer cells.European journal of immunology · 2019Article
- Expansion of Human NK Cells Using K562 Cells Expressing OX40 Ligand and Short Exposure to IL-21.Frontiers in immunology · 2019Article
- 2B4 Mediates Inhibition of CD8Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- The Emerging Role of CD244 Signaling in Immune Cells of the Tumor Microenvironment.Frontiers in immunology · 2018Review
- Article
- Preventive Anti-CD2 Treatment does not Impair Parasite Control in a Murine Toxoplasmosis Model.European journal of microbiology & immunology · 2015Article
- The DC-SIGN-CD56 interaction inhibits the anti-dendritic cell cytotoxicity of CD56 expressing cells.Infectious agents and cancer · 2015Article
- Article
- Differential expression of proteins in naïve and IL-2 stimulated primary human NK cells identified by global proteomic analysis.Journal of proteomics · 2013Article
- Evolving immune circuits are generated by flexible, motile, and sequential immunological synapses.Immunological reviews · 2013Review
- Augmentation of natural cytotoxicity by chronic low-dose ionizing radiation in murine natural killer cells primed by IL-2.Journal of radiation research · 2012Article
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human natural killer (NK) cells express an abundant level of 2B4 and CD2 on their surface. Their counter-receptors, CD48 and CD58, are also expressed on the NK cell surface, raising a question about the functional consequences of potential 2B4/CD48 and CD2/CD58 interactions. Using blocking antibodies specific to each receptor, we demonstrated that both 2B4/CD48 and CD2/CD58 interactions were essential for the development of NK effector functions: cytotoxicity and cytokine secretion. However, only 2B4/CD48, but not CD2/CD58, interactions were shown to be critical for the optimal NK cell proliferation in response to interleukin (IL)-2. IL-2-activated NK cells cultured in the absence of 2B4/CD48 or CD2/CD58 interactions were severely impaired for their ability to induce intracellular calcium mobilization and subsequent ERK activation upon tumor target exposure, suggesting that the early signaling pathway of NK receptors leading to impaired cytolysis and interferon (IFN)-γ secretion was inhibited. Nevertheless, these defects did not fully account for the reduced proliferation of NK cells in the absence of 2B4/CD48 interactions, because anti-CD2 or anti-CD58 monoclonal antibody (mAb)-treated NK cells, showing defective signaling and effector functions, displayed normal proliferation upon IL-2 stimulation. These results propose the signaling divergence between pathways leading to cell proliferation and cytotoxicity/cytokine release, which can be differentially regulated by 2B4 and CD2 during IL-2-driven NK cell activation. Collectively, these results reveal the importance of homotypic NK-to-NK cell cross-talk through 2B4/CD48 and CD2/CD58 pairs and further present their differential and overlapping roles in human NK cells.
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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.