title: Interleukin-21 activates human natural killer cells and modulates their surface receptor expression.
abstract: Interleukin (IL)-21 is a novel cytokine that has been shown to enhance proliferation and activation of CD8+ T cells, enhance natural killer (NK) cell activity and costimulate anti-CD40-driven B-cell proliferation in mice. Several studies have furthermore demonstrated antitumour effects of IL-21 administration in mouse models. In this study we have investigated how IL-21 affects the survival and cytotoxicity of human NK cells and modulates their expression of surface receptors and of the effector molecules granzyme B and perforin. In contrast to murine NK cells, where IL-21 alone cannot sustain survival, IL-21 and IL-2 were equally efficient in sustaining survival of human NK cells. In the absence of other cytokines, IL-21 had little effect on expression of a panel of surface receptors on human NK cells. However, IL-21 synergized with IL-2 to up-regulate several surface receptors, including NKG2A, CD25, CD86 and CD69. The CD25+ CD86+ NK cells were CD56(bright) and were large and granular. Expression of the effector molecules perforin and granzyme A and B was up-regulated by IL-21 at both mRNA and protein levels. Furthermore, IL-21 increased the cytotoxicity of NK cells against K562 target cells. These findings suggest that IL-21 modulates NK cell activity through induction of intracellular effector molecules as well as modulation of surface receptor expression.
authors.affiliation: Cancer Pharmacology, Novo Nordisk A/S, Måløv, Denmark. skak@novonordisk.com
authors.forename: Kresten
authors.initials: K
authors.lastname: Skak
authors.forename: Klaus Stensgaard
authors.initials: KS
authors.lastname: Frederiksen
authors.forename: Dorthe
authors.initials: D
authors.lastname: Lundsgaard
mesh_terms: D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000276:immunology; D007378:Interleukins / Q000276:immunology*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D011971:Receptors, Immunologic / Q000378:metabolism*; D000098546:Interleukin-21
chemical_list: D007376:Interleukin-2; D007378:Interleukins; D011971:Receptors, Immunologic; D000098546:Interleukin-21