title: Down regulation of human natural killer cell-mediated cytolysis induced by blood transfusion: role of transforming growth factor-β(1), soluble Fas ligand, and soluble Class I human leukocyte antigen.
abstract: BACKGROUND
  Human natural killer (NK) cells are thought to play a role in antiviral response and tumor immune surveillance. The molecular mechanisms of down regulation of NK-cell activity observed after red blood cell (RBC) transfusion is still undefined.
  
  
  METHODS
  Both effects of blood transfusion (ex vivo) and supernatants (SNs) derived from RBC units unstored (RBC-0) or stored for 5 or 30 days (RBC-5 or -30, respectively) in vitro were analyzed on NK cell-mediated cytolytic activity.
  
  
  RESULTS
  We have found that NK cells isolated from transfused patients on Day 3 lysed the NK-sensitive target cells K562 to a lesser extent than before transfusion. This down regulation of NK-cell activation was evident also for NK-cell killing mediated through the engagement of NK cell-activating receptors as NKG2D, NKp30, NKp46, and CD16. Transfused patients reacquired NK cell-mediated cytolytic activity from Day 5 to Day 7 after transfusion. SN from RBC-30, but not from RBC-0 or RBC-5, strongly inhibited the generation of lymphokine-activated killer (LAK) cells and lysis of the NK-resistant target cell Jurkat in a dose-dependent manner. Transforming growth factor-β1 (TGF-β1) blocking antibodies partially restored the generation of LAK activity. In addition, the depletion of both soluble Class I human leukocyte antigens (sHLA-I) and soluble Fas ligand (sFasL) from SN of RBC-30 completely restored the generation of LAK activity.
  
  
  CONCLUSIONS
  Altogether, these findings would support the idea that blood transfusion-mediated down regulation of NK-cell activity is mediated by sHLA-I, sFasL, and TGF-β1.
authors.affiliation: Laboratory of Clinical Immunology, Azienda Ospedaliera Universitaria San Martino-DIMI, Genoa, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Ghio
authors.forename: Paola
authors.initials: P
authors.lastname: Contini
authors.forename: Simone
authors.initials: S
authors.lastname: Negrini
authors.forename: Clemente
authors.initials: C
authors.lastname: Mazzei
authors.forename: Maria R
authors.initials: MR
authors.lastname: Zocchi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Poggi
mesh_terms: D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology*; D053222:Fas Ligand Protein / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000276:immunology; D065227:Transfusion Reaction
chemical_list: D053222:Fas Ligand Protein; D015395:Histocompatibility Antigens Class I; D053773:Transforming Growth Factor beta1