PMID:14764669

Citation	Brady, J, Hayakawa, Y, Smyth, MJ and Nutt, SL (2004) IL-21 induces the functional maturation of murine NK cells. J. Immunol. 172:2048-58
Abstract	IL-21 is a recently identified cytokine that stimulates mouse NK cell effector functions in vitro. In this study we demonstrate that IL-21 achieves its stimulatory effect by inducing the development of mature NK cells into a large granular lymphocyte phenotype with heightened effector function. IL-21 treatment results in increased cell size and granularity and a corresponding decrease in cell viability and proliferative potential. These cells up-regulate the expression of the inhibitory CD94-NKG2A receptor complex and the activation markers CD154 and killer cell, lectin-like-receptor G1. Surprisingly, IL-21 treatment also results in down-regulation of the pan-NK marker, NK1.1. Coinciding with these cellular changes IL-21 enhances cytolytic capacity across a spectrum of target sensitivities and induces IL-10 and IFN-gamma production. In vivo treatment with IL-21 results in a very similar activation and phenotypic maturation of NK cells as well as a potent increase in NK cell-mediated anti-tumor immunity that is perforin dependent. These developmental changes suggested that IL-21 functions to induce the terminal differentiation of mouse NK cells, resulting in heightened NK cell-mediated cytotoxicity and immune surveillance.
Links	PubMed
Keywords	Animals; Antigens/biosynthesis; Antigens, Ly; Antigens, Surface; Biological Markers/analysis; Cell Differentiation/immunology; Cell Line, Tumor; Cell Membrane/immunology; Cell Membrane/metabolism; Cells, Cultured; Cytokines/biosynthesis; Cytokines/secretion; Cytotoxicity, Immunologic/immunology; Down-Regulation/immunology; Growth Inhibitors/administration & dosage; Growth Inhibitors/physiology; Immunophenotyping; Interleukin-15/physiology; Interleukin-2/physiology; Interleukins/administration & dosage; Interleukins/physiology; Killer Cells, Natural/cytology; Killer Cells, Natural/immunology; Killer Cells, Natural/metabolism; Killer Cells, Natural/secretion; Lectins, C-Type; Liver Neoplasms/immunology; Liver Neoplasms/prevention & control; Liver Neoplasms/secondary; Lymphocyte Activation/immunology; Lymphocyte Subsets/immunology; Lymphocyte Subsets/metabolism; Melanoma, Experimental/immunology; Melanoma, Experimental/prevention & control; Melanoma, Experimental/secondary; Membrane Glycoproteins/deficiency; Membrane Glycoproteins/genetics; Membrane Glycoproteins/physiology; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; NK Cell Lectin-Like Receptor Subfamily B; Perforin; Pore Forming Cytotoxic Proteins; Protein Biosynthesis; Proteins/antagonists & inhibitors
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