title: Impaired Immunosuppressive Effect of Bronchoalveolar Mesenchymal Stem Cells in Hypersensitivity Pneumonitis: Preliminary Findings.
abstract: Bronchoalveolar mesenchymal stem cells (MSCs) play an important role in the maintenance of lung integrity. Therapeutic application of bone marrow-derived MSCs reduced chronic bronchial inflammation in idiopathic pulmonary fibrosis, and improved the ratio of survivors in sepsis with pneumonia. This study investigated the effect of MSCs from bronchoalveolar lavage fluid (BALF) of hypersensitivity pneumonitis (HP) on T-cell function under in vitro conditions.
  
  
  
  Bronchoalveolar MSCs were obtained via bronchoscopy with BAL from children with severe subacute HP. As control, BALF MSCs were assessed from children without any inflammatory lung disease. Isolated MSCs were characterized via immunophenotyping by flow cytometry and confocal laser scanning microscopy. HP-derived and healthy separated peripheral blood mononuclear cells (PBMCs) were stimulated by 5 µg/mL phytohemagglutinin in the presence of HP-derived or control MSCs in 5-day cultures. Proliferation and activation of T-cells were characterized by the mean fluorescence intensity (MFI) of 5,6-carboxyfluorescein-diacetat succinimidyl ester (CFSE) and CD25, CD69 as well as HLA-DR surface positivities, respectively.
  
  
  
  HP-derived MSCs showed significantly lower level of CD73, CD90, and CD105 expression compared to control MSCs in both flow cytometric and confocal microscopic experiments. MSCs from HP did not reduce T-cell proliferation based on CFSE MFI values, while the level of CD25 expression on both control and HP-derived CD4+ and CD8+ T-cells was significantly reduced by normal MSCs, while HP-derived MSCs did not have any significant effect. The level of other activation markers was not markedly modulated by MSCs.
  
  
  
  BALF MSCs from HP are unable to downregulate the proliferation and activation of T-cells that may support the development of recurrent intrapulmonary inflammation in HP. © 2016 International Clinical Cytometry Society.
authors: Department of Internal Medicine, Division of Nephrology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: Enikő
authors: E
authors: Balogh
authors: Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: Béla
authors: B
authors: Nagy
authors: Department of Internal Medicine, Division of Nephrology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: Ágnes
authors: Á
authors: Gyetvai
authors: Department of Pediatrics, Division of Pulmonology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: Zsolt
authors: Z
authors: Bene
authors: Department of Pathology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: Zoltán
authors: Z
authors: Hendrik
authors: Department of Internal Medicine, Division of Nephrology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.|MTA-DE Vascular Biology, Thrombosis and Hemostasis Research Group, Hungarian Academy of Sciences, Debrecen, Hungary.
authors: Viktória
authors: V
authors: Jeney
authors: Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: Péter
authors: P
authors: Nagy
authors: Department of Pediatrics, Division of Pulmonology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: Ágnes
authors: Á
authors: Papp
authors: Department of Internal Medicine, Division of Nephrology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.|MTA-DE Vascular Biology, Thrombosis and Hemostasis Research Group, Hungarian Academy of Sciences, Debrecen, Hungary.
authors: József
authors: J
authors: Balla
authors: Department of Pediatrics, Division of Pulmonology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.|MTA-DE Vascular Biology, Thrombosis and Hemostasis Research Group, Hungarian Academy of Sciences, Debrecen, Hungary.
authors: György
authors: G
authors: Balla
authors: Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: János
authors: J
authors: Kappelmayer
authors: Department of Pediatrics, Division of Pulmonology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: Béla
authors: B
authors: Nagy
mesh_terms: D000542:Alveolitis, Extrinsic Allergic / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D049109:Cell Proliferation / Q000502:physiology; D002648:Child; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D007249:Inflammation / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000473:pathology*
keywords: T-lymphocyte proliferation and activation; bronchoalveolar lavage; hypersensitivity pneumonitis; mesenchymal stem cells