title: Differential effects of mycophenolate mofetil and cyclosporine A on peripheral blood and cord blood natural killer cells activated with interleukin-2.
abstract: OBJECTIVE
  Graft-versus-host disease remains a major cause of death after hematopoietic stem cell transplantation. Cyclosporine (CsA) and mycophenolate mofetil (MMF) have been successfully used alone or in combination as prophylaxis for graft-versus-host disease. Although the effects of these drugs on T cells have been studied, little is known about the effects of both drugs on natural killer (NK) cells. We examined if the sensitivity of umbilical cord blood (CB) NK cells to MMF and/or CsA differs from their adult counterparts.
  
  
  METHODS
  An approach that was based on flow cytometry and real-time polymerase chain reaction was used to assess the effects of MMF, CsA and the combination of both drugs on the viability, activation, proliferation and cytotoxicity of peripheral blood (PB) and CB NK cells after culture with interleukin-2.
  
  
  RESULTS
  MMF alone or together with CsA induced cell death of CB NK cells but not of PB NK cells. MMF and CsA had differential effects on NK cell activation but significantly reduced proliferation of CB NK cells. MMF reduced perforin expression by PB NK cells, whereas CsA alone or together with MMF drastically decreased degranulation of CB and PB NK cells. However, neither affected cytokine secretion by PB and CB NK cells.
  
  
  CONCLUSIONS
  This study showed that CB NK cells were more sensitive to MMF and CsA than were PB NK cells. MMF and CsA had significant effects on NK cells that could jeopardize the beneficial effects of NK cells after hematopoietic stem cell transplantation.
authors: Anthony Nolan Research Institute and University College London, Royal Free Campus, London, United Kingdom.
authors: Sophie
authors: S
authors: Derniame
authors: Anthony Nolan Research Institute and University College London, Royal Free Campus, London, United Kingdom.
authors: Juliana
authors: J
authors: Perazzo
authors: Anthony Nolan Research Institute and University College London, Royal Free Campus, London, United Kingdom.
authors: Fuiyee
authors: F
authors: Lee
authors: Anthony Nolan Research Institute and University College London, Royal Free Campus, London, United Kingdom.
authors: Anna
authors: A
authors: Domogala
authors: Anthony Nolan Research Institute and University College London, Royal Free Campus, London, United Kingdom.
authors: Michelle
authors: M
authors: Escobedo-Cousin
authors: Anthony Nolan Research Institute and University College London, Royal Free Campus, London, United Kingdom.
authors: Rehab
authors: R
authors: Alnabhan
authors: Anthony Nolan Research Institute and University College London, Royal Free Campus, London, United Kingdom.
authors: Martha
authors: M
authors: Luevano
authors: Anthony Nolan Research Institute and University College London, Royal Free Campus, London, United Kingdom.
authors: Isabela
authors: I
authors: Pedroza-Pacheco
authors: Haematology Department, Hammersmith Hospital, London, United Kingdom.
authors: Nichola
authors: N
authors: Cooper
authors: Anthony Nolan Research Institute and University College London, Royal Free Campus, London, United Kingdom.
authors: Alejandro
authors: A
authors: Madrigal
authors: Anthony Nolan Research Institute and University College London, Royal Free Campus, London, United Kingdom. Electronic address: aurore.saudemont@anthonynolan.org.
authors: Aurore
authors: A
authors: Saudemont
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007231:Infant, Newborn; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D011247:Pregnancy
chemical_list: D007376:Interleukin-2; D016572:Cyclosporine; D009173:Mycophenolic Acid
keywords: cord blood; cyclosporine A; mycophenolate mofetil; natural killer cells