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International Immunology Advance Access originally published online on November 15, 2005
International Immunology 2006 18(1):49-58; doi:10.1093/intimm/dxh348
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© The Japanese Society for Immunology. 2005. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

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

Sonia A. Perez1, Louisa G. Mahaira1, Panagiota A. Sotiropoulou1, Angelos D. Gritzapis1, Eleni G. Iliopoulou1, Dimitrios K. Niarchos1, Nike T. Cacoullos1, Yannis G. Kavalakis2, Aris I. Antsaklis2, Nectaria N. Sotiriadou1, Constantin N. Baxevanis1 and Michael Papamichail1

1 Cancer Immunology and Immunotherapy Center, Saint Savas Hospital, 171 Alexandras Avenue, Athens 115 22, Greece
2 1st Obstetrics and Gynecology University Clinic, Alexandras Maternity Hospital, Athens, Greece

Correspondence to: S. Perez; E-mail: perez{at}ciic.gr

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.

Keywords: CD34, CD56, hydrocortisone, IL-21R

Transmitting editor: M. Reth


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