title: Inhibition of term decidual NK cell cytotoxicity by soluble HLA-G1.
abstract: OBJECTIVE
  Soluble (s)HLA-G1 is produced by trophoblast cells. Aim was to analyze the capacities and mechanisms of sHLA-G1 to regulate interleukin (IL)-2-induced cytotoxicity of natural killer (NK) cells from human deciduas.
  
  
  METHODS
  Natural killer cells were isolated from decidual layers of term placentae, stimulated or not with IL-2 and supplemented with various concentrations of recombinant soluble HLA-G1 (sHLA-G1). For NK cell cytotoxicity assays, K562 cells were used as targets. Expression of signal transducer and activator of transcription 3 (STAT3) and perforin was analyzed by Western blotting. Apoptosis was examined by assessment of poly(ADP-ribose) polymerase cleavage. NK cells were analyzed by flow cytometry for IL-2receptor-alpha (IL-2R alpha; CD25) and transferrin receptor CD71 expression.
  
  
  RESULTS
  Interleukin-2 increases CD71, STAT3, perforin expression and cytotoxic potential of NK cells. Expression of CD71, STAT3 and perforin decreased simultaneously with cytotoxicity and dose-dependently when sHLA-G1 (1.6 micro g/mL-1.6 ng/mL) was added to IL-2 stimulated cultures. sHLA-G1 did not induce apoptosis and CD25 expression was not affected.
  
  
  CONCLUSIONS
  Interleukin-2R alpha expression is not controlled by sHLA-G1, but its signal transducer STAT3 as well as several downstream effects, such as perforin expression, proliferation and cytotoxicity. The control of STAT3 bioavailability through sHLA-G1 may be a key regulator of the mentioned effects.
authors.affiliation: Placenta-Labor, Department of Obstetrics, Friedrich-Schiller-University, Jena, Germany.
authors.forename: Tobias G
authors.initials: TG
authors.lastname: Poehlmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Schaumann
authors.forename: Susann
authors.initials: S
authors.lastname: Busch
authors.forename: Justine S
authors.initials: JS
authors.lastname: Fitzgerald
authors.forename: Marise
authors.initials: M
authors.lastname: Aguerre-Girr
authors.forename: Philippe
authors.initials: P
authors.lastname: Le Bouteiller
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Schleussner
authors.forename: Udo R
authors.initials: UR
authors.lastname: Markert
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects* / Q000276:immunology; D003656:Decidua / Q000187:drug effects / Q000276:immunology*; D005260:Female; D006680:HLA Antigens / Q000276:immunology* / Q000494:pharmacology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D054353:Perforin; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D052899:Pore Forming Cytotoxic Proteins / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012995:Solubility; D047929:Term Birth / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; C068126:CD71 antigen; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D011990:Receptors, Transferrin; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D054353:Perforin; D011065:Poly(ADP-ribose) Polymerases