Effect of IL-21 on NK cells derived from different umbilical cord blood populations

Int Immunol. 2006 Jan;18(1):49-58. doi: 10.1093/intimm/dxh348. Epub 2005 Nov 15.


IL-21 plays a role in the proliferation and maturation of NK cells developed from hematopoietic stem cells. In this study, we found that IL-21, in the presence of physiological concentration of hydrocortisone (HC), has a significant impact on the functions of NK cells derived from umbilical cord blood (CB) populations. We demonstrate that IL-21, in combination with Flt3-ligand, IL-15 and HC, induces high proliferative responses and, apart from enhancing NK-mediated cytotoxicity, it also induces a significant increase in lymphokine-activated killer activity of CB/CD34+-derived CD56+ cells. In addition, IL-21 induced changes in the CD56+ cell cytokine secretion profile. Thus, we observed increased levels of IL-10 and granulocyte macrophage colony-stimulating factor, whereas tumor necrosis factor-alpha levels decreased. IFN-gamma production was also modified by IL-21, depending on the presence or absence of IL-18. CB/CD34+ cells did not express the IL-21R ex vivo, but receptor expression was induced during their commitment to differentiation into CD56+ cells. Our data ascribe to IL-21 an essential role on NK cell development and function under conditions similar to the in vivo CB microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / immunology
  • Anti-Inflammatory Agents / pharmacology
  • Antigens, CD34 / immunology
  • CD56 Antigen / immunology
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cytokines / immunology
  • Fetal Blood / cytology
  • Fetal Blood / immunology*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology*
  • Humans
  • Hydrocortisone / immunology
  • Hydrocortisone / pharmacology
  • Interleukin-21 Receptor alpha Subunit
  • Interleukins / immunology*
  • Interleukins / pharmacology
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology*
  • Membrane Proteins / immunology
  • Receptors, Interleukin / immunology
  • Receptors, Interleukin-21


  • Anti-Inflammatory Agents
  • Antigens, CD34
  • CD56 Antigen
  • Cytokines
  • IL21R protein, human
  • Interleukin-21 Receptor alpha Subunit
  • Interleukins
  • Membrane Proteins
  • Receptors, Interleukin
  • Receptors, Interleukin-21
  • flt3 ligand protein
  • interleukin-21
  • Hydrocortisone