Effect of IL-21 on NK cells derived from different umbilical cord blood populations.
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.
Perez
Sonia A
SA
Cancer Immunology and Immunotherapy Center, Saint Savas Hospital, 171 Alexandras Avenue, Athens 115 22, Greece. perez@ciic.gr
Mahaira
Louisa G
LG
Sotiropoulou
Panagiota A
PA
Gritzapis
Angelos D
AD
Iliopoulou
Eleni G
EG
Niarchos
Dimitrios K
DK
Cacoullos
Nike T
NT
Kavalakis
Yannis G
YG
Antsaklis
Aris I
AI
Sotiriadou
Nectaria N
NN
Baxevanis
Constantin N
CN
Papamichail
Michael
M
D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000494:pharmacology; D018952:Antigens, CD34 / Q000276:immunology; D019002:CD56 Antigen / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D006854:Hydrocortisone / Q000276:immunology / Q000494:pharmacology; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins / Q000276:immunology* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology; D018123:Receptors, Interleukin / Q000276:immunology; D053655:Receptors, Interleukin-21; D000098546:Interleukin-21
D000893:Anti-Inflammatory Agents; D018952:Antigens, CD34; D019002:CD56 Antigen; D016207:Cytokines; C508117:IL21R protein, human; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins; D008565:Membrane Proteins; D018123:Receptors, Interleukin; D053655:Receptors, Interleukin-21; C084881:flt3 ligand protein; D000098546:Interleukin-21; D006854:Hydrocortisone