GENE-EXPRESSION AND SECRETION OF CYTOKINES AND CYTOKINE RECEPTORS FROM HIGHLY PURIFIED CD56-KILLER-CELLS STIMULATED WITH INTERLEUKIN-2, INTERLEUKIN-7 AND INTERLEUKIN-12( NATURAL)

Interleukin (IL)-2 IL-7 and IL-12 stimulate the generation of lymphoki ne-activated killer activity and proliferation in natural killer (NK) cells by different mechanisms. In this study,we have compared the abil ity of IL-2, IL-7 and IL-12 to induce expression of cytokines and cyto kine receptors both at the gene and protein level. IL-2 and IL-12 stim ulated the CD56+ NK cells to release significant amounts of soluble p5 5 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 induc tion was observed after cytokine-stimulation. Compared to the effects of IL-2, IL-7 induced lower, but substantial levels of granulocyte-mac rophage colony-stimulating factor (GM-CSF) mRNA, and IL-7 was a more p otent GM-CSF-inducing stimulus than IL-12. IL-12 induced higher levels of interferon-gamma (IFN-gamma) mRNA than did IL-2, and IL-7 only wea kly influenced the IFN-gamma expression. In accordance with the mRNA s tudies, IL-7 induced the secretion of high amounts of GM-CSF and no or low levels of IFN-gamma, whereas high amounts of IFN-gamma and low le vels of GM-CSF were detected in supernatants from IL-12-stimulated NK cells. In conclusion, IL-2, IL-7 and IL-12 differentially regulate exp ression of cytokines and cytokine receptors both at the gene and prote in level.