Gene expression and secretion of cytokines and cytokine receptors from highly purified CD56+ natural killer cells stimulated with interleukin‐2, interleukin‐7 and interleukin‐12

Abstract

Interleukin (IL)‐2 IL‐7 and IL‐12 stimulate the generation of lymphokine‐activated killer activity and proliferation in natural killer (NK) cells by different mechanisms. In this study, we have compared the ability of IL‐2, IL‐7 and IL‐12 to induce expression of cytokines and cytokine receptors both at the gene and protein level. IL‐2 and IL‐12 stimulated the CD56⁺ NK cells to release significant amounts of soluble p55 and p75 tumor necrosis factor receptor (TNFR), whereas less amounts of soluble TNFR were detected in IL‐7‐stimulated cultures. The p55 and p75 TNFR mRNA were expressed in resting NK cells, and no further induction was observed after cytokine‐stimulation. Compared to the effects of IL‐2, IL‐7 induced lower, but substantial levels of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) mRNA, and IL‐7 was a more potent GM‐CSF‐inducing stimulus than IL‐12. IL‐12 induced higher levels of interferon‐γ (IFN‐γ) mRNA than did IL‐2, and IL‐7 only weakly influenced the IFN‐γ expression. In accordance with the mRNA studies, IL‐7 induced the secretion of high amounts of GM‐CSF and no or low levels of IFN‐γ, whereas high amounts of IFN‐γ and low levels of GM‐CSF were detected in supernatants from IL‐12‐stimulated NK cells. In conclusion, IL‐2, IL‐7 and IL‐12 differentially regulate expression of cytokines and cytokine receptors both at the gene and protein level.