title: Differential activation of cord blood and peripheral blood natural killer cells by cytokines.
abstract: OBJECTIVE
  Natural killer (NK) cells play important roles in the clearance of infection and transformed cells. Cord blood (CB) is currently used as a source of hematopoietic stem cells for transplantation and is a potential source of NK cells for immunotherapy. We previously showed that CB NK cells are immature and less cytotoxic as compared with peripheral blood (PB) NK cells. We aimed to identify which cytokines, among interleukin (IL)-2, IL-12, IL-15 and IL-18 and their combinations, could fully activate CB NK cells as compared with PB NK cells.
  
  
  METHODS
  We performed a comprehensive analysis of phenotype and functionality of cytokine-activated NK cells.
  
  
  RESULTS
  Our results show that the lower responsiveness of CB NK cells to IL-2 is associated with lower levels of expression of IL-2 receptors and decreased phosphorylation of STAT5 as compared with PB NK cells. Activation of CB NK cells with IL-15+18 led to the most robust proliferative response and higher interferon-γ and tumor necrosis factor-α secretion, whereas activation with IL-15+2 promoted enhanced cytotoxicity. PB NK cells responded significantly better to IL-2 than to CB NK cells but were also fully activated with other cytokine treatments including IL-15, IL-15+2 or IL-15+18. It was also possible to use cytokines to generate memory-like NK cells, with sustained ability to produce interferon-γ, from both CB and PB.
  
  
  CONCLUSIONS
  CB NK cells are fully functional on activation with IL-15+2 or IL-15+18 rather than IL-2 alone as observed for PB NK cells. These cytokines should be considered in the future to activate CB NK cells for therapeutic purposes.
authors.affiliation: University College London, Cancer Institute, Royal Free Campus, London, United Kingdom; Anthony Nolan Research Institute, Royal Free Campus, London, United Kingdom.
authors.forename: Rehab
authors.initials: R
authors.lastname: Alnabhan
authors.affiliation: University College London, Cancer Institute, Royal Free Campus, London, United Kingdom; Anthony Nolan Research Institute, Royal Free Campus, London, United Kingdom.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Madrigal
authors.affiliation: University College London, Cancer Institute, Royal Free Campus, London, United Kingdom; Anthony Nolan Research Institute, Royal Free Campus, London, United Kingdom. Electronic address: aurore.saudemont@anthonynolan.org.
authors.forename: Aurore
authors.initials: A
authors.lastname: Saudemont
mesh_terms: D016207:Cytokines / Q000276:immunology*; D005312:Fetal Blood / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology*; D010641:Phenotype; D014470:Umbilical Cord / Q000166:cytology
chemical_list: D016207:Cytokines
keywords: cord blood; cytokine activation; memory-like NK cells; natural killer cells