Abstract
2B4 (CD244) and its ligand, CD48, are expressed on all natural killer (NK) cells. In studies using 2B4-deficient, CD48-deficient, or wild-type NK cells with blocking antibodies, we found that in the absence of 2B4-CD48 interactions, activated murine NK cells kill each other. We also show that NK-NK fratricide in the absence of 2B4-CD48 interaction is dependent on perforin both in vitro and in vivo. 2B4 has been reported to have activating, costimulatory, and inhibitory functions on murine NK cells. 2B4-mediated inhibition of NK-cell fratricide explains some of the paradoxes of 2B4 function reported in studies of murine NK cells. We show that in the absence of 2B4 signaling, activated NK cells have defective cytotoxicity and proliferation because of fratricide and not due to the absence of a 2B4-dependent activation signal.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antigens, CD / genetics
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Antigens, CD / physiology*
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CD48 Antigen
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Cell Proliferation*
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Cell Survival*
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Chromium / metabolism
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Homeodomain Proteins / genetics
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Homeodomain Proteins / physiology
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Killer Cells, Lymphokine-Activated / immunology*
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Killer Cells, Lymphokine-Activated / metabolism
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism
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Lymphocyte Activation / genetics
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Knockout
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Neoplasms / genetics
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Neoplasms / immunology
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Pore Forming Cytotoxic Proteins / genetics
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Pore Forming Cytotoxic Proteins / physiology
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Receptors, Immunologic / genetics
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Receptors, Immunologic / physiology*
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Signaling Lymphocytic Activation Molecule Family
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beta 2-Microglobulin / genetics
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beta 2-Microglobulin / physiology
Substances
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Antigens, CD
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CD48 Antigen
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Cd244a protein, mouse
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Cd48 protein, mouse
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Homeodomain Proteins
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Membrane Glycoproteins
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Pore Forming Cytotoxic Proteins
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Receptors, Immunologic
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Signaling Lymphocytic Activation Molecule Family
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beta 2-Microglobulin
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perforin, mouse
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Chromium
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RAG-1 protein