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

Eur J Immunol. 1993 Aug;23(8):1831-8. doi: 10.1002/eji.1830230815.

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-gamma (IFN-gamma) mRNA than did IL-2, and IL-7 only weakly influenced the IFN-gamma 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-gamma, whereas high amounts of IFN-gamma 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / analysis*
  • Antigens, Differentiation, T-Lymphocyte / analysis*
  • Base Sequence
  • CD56 Antigen
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Gene Expression / drug effects
  • Humans
  • Interleukin-12
  • Interleukin-2 / pharmacology
  • Interleukin-7 / pharmacology
  • Interleukins / pharmacology*
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Molecular Sequence Data
  • Receptors, Cell Surface / biosynthesis*
  • Receptors, Cell Surface / genetics
  • Receptors, Interleukin-2 / biosynthesis*
  • Receptors, Interleukin-2 / genetics
  • Receptors, Tumor Necrosis Factor

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD56 Antigen
  • Cytokines
  • Interleukin-2
  • Interleukin-7
  • Interleukins
  • Receptors, Cell Surface
  • Receptors, Interleukin-2
  • Receptors, Tumor Necrosis Factor
  • Interleukin-12