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. |