Abstract
A lymphocyte subpopulation, the Valpha14 natural killer T (NKT) cells, expresses both NK1.1 and a single invariant T cell receptor encoded by the Valpha14 and Jalpha281 gene segments. Mice with a deletion of the Jalpha281 gene segment were found to exclusively lack this subpopulation. The Valpha14 NKT cell-deficient mice could no longer mediate the interleukin-12 (IL-12)-induced rejection of tumors. Although the antitumor effect of IL-12 was thought to be mediated through natural killer cells and T cells, Valpha14 NKT cells were found to be an essential target of IL-12, and they mediated their cytotoxicity by an NK-like effector mechanism after activation with IL-12.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Bacterial Agents / pharmacology
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Cytotoxicity, Immunologic*
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Gene Deletion
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Gene Targeting
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Genes, RAG-1
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Genes, T-Cell Receptor alpha
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Interferon-gamma / immunology
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Interleukin-12 / immunology*
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Killer Cells, Natural / immunology*
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Macrolides*
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Melanoma, Experimental / immunology
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Neoplasms, Experimental / immunology*
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Poly I-C / pharmacology
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Proton-Translocating ATPases / antagonists & inhibitors
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, Antigen, T-Cell, alpha-beta / immunology*
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T-Lymphocyte Subsets / immunology*
Substances
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Anti-Bacterial Agents
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Macrolides
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Receptors, Antigen, T-Cell, alpha-beta
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Interleukin-12
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concanamycin A
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Interferon-gamma
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Proton-Translocating ATPases
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Poly I-C