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Publication : IL-21 induces the functional maturation of murine NK cells.

First Author  Brady J Year  2004
Journal  J Immunol Volume  172
Issue  4 Pages  2048-58
PubMed ID  14764669 Mgi Jnum  J:88003
Mgi Id  MGI:3028812 Doi  10.4049/jimmunol.172.4.2048
Citation  Brady J, et al. (2004) IL-21 induces the functional maturation of murine NK cells. J Immunol 172(4):2048-58
abstractText  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.
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