PRODUCTION OF IL-5 BY HUMAN NK CELLS AND REGULATION OF IL-5 SECRETIONBY IL-4, IL-10, AND IL-12

Human NK cells produce IFN-gamma, TNF-alpha, and granulocyte macrophag e-CSF when stimulated with susceptible target cells or through the CD1 6 and CD94 cell surface molecules. This study reports that NK cells al so produce IL-5, a cytokine typically produced by Th2 cells, which med iates mobilization and differentiation of eosinophils. Polyclonal NK c ell populations and NK cell clones produce IL-5 when stimulated to pro liferate with gamma-irradiated MM-170 melanoma cells or JY B-lymphobla stoid cells and rlL-2. IL-5 is produced in cultures generated from fre shly isolated NK cells (primary cultures) and when quiescent NK cells from primary cultures are restimulated to proliferate (secondary cultu res). Production of IL-5 is on average 8.8-fold greater in secondary c ultures compared with primary cultures (n > 18), suggesting that the a bility of NK cells to produce IL-5 matures during primary stimulation. IL-5 secretion, particularly in primary cultures, is augmented by IL- 4 and is inhibited by IL-12 and IL-10. By contrast, IL-4 and IL-12 hav e the reverse effects on IFN-gamma secretion. Cultured NK cells that n o longer secrete cytokines can be restimulated to do so with either ph orbol 12,13 dibutyrate and ionomycin or with susceptible target cells in the presence of rlL-2. IL-5 production in these cultures occurs onl y when NK cells are in an exponential growth phase, whereas IFN-gamma, TNF-alpha, and granulocyte macrophage-CSF are produced also by stimul ation of quiescent cells, although to a lesser extent. Furthermore, cy tokine production is unrelated to the cytolytic activity of NK cells. In conclusion, proliferating human NK cells have the potential to prod uce IL-5 with secretion regulated by IL-4, IL-10, and IL-12.