Impaired immunosuppressive effect of bronchoalveolar mesenchymal stem cells in hypersensitivity pneumonitis: Preliminary findings

Eniko a. Balogh, B. Nagy, Ágnes Gyetvai, Zsolt Bene, Zoltán Hendrik, Viktória Jeney, Péter Nagy, Ágnes Papp, J. Balla, György Balla, János Kappelmayer, Béla Nagy

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish
JournalCytometry Part B - Clinical Cytometry
DOIs
Publication statusAccepted/In press - 2016

Fingerprint

Extrinsic Allergic Alveolitis
Immunosuppressive Agents
Mesenchymal Stromal Cells
T-Lymphocytes
Bronchoalveolar Lavage Fluid
Esters
Fluorescence
Inflammation
Dimercaprol
Immunophenotyping
Idiopathic Pulmonary Fibrosis
Bronchoscopy
Phytohemagglutinins
HLA-DR Antigens
Confocal Microscopy

Keywords

  • Bronchoalveolar lavage
  • Hypersensitivity pneumonitis
  • Mesenchymal stem cells
  • T-lymphocyte proliferation and activation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

Cite this

Impaired immunosuppressive effect of bronchoalveolar mesenchymal stem cells in hypersensitivity pneumonitis : Preliminary findings. / Balogh, Eniko a.; Nagy, B.; Gyetvai, Ágnes; Bene, Zsolt; Hendrik, Zoltán; Jeney, Viktória; Nagy, Péter; Papp, Ágnes; Balla, J.; Balla, György; Kappelmayer, János; Nagy, Béla.

In: Cytometry Part B - Clinical Cytometry, 2016.

Research output: Contribution to journalArticle

Balogh, Eniko a. ; Nagy, B. ; Gyetvai, Ágnes ; Bene, Zsolt ; Hendrik, Zoltán ; Jeney, Viktória ; Nagy, Péter ; Papp, Ágnes ; Balla, J. ; Balla, György ; Kappelmayer, János ; Nagy, Béla. / Impaired immunosuppressive effect of bronchoalveolar mesenchymal stem cells in hypersensitivity pneumonitis : Preliminary findings. In: Cytometry Part B - Clinical Cytometry. 2016.
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abstract = "Background: 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. Methods: 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. Results: 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. Conclusions: 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.",
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author = "Balogh, {Eniko a.} and B. Nagy and {\'A}gnes Gyetvai and Zsolt Bene and Zolt{\'a}n Hendrik and Vikt{\'o}ria Jeney and P{\'e}ter Nagy and {\'A}gnes Papp and J. Balla and Gy{\"o}rgy Balla and J{\'a}nos Kappelmayer and B{\'e}la Nagy",
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T1 - Impaired immunosuppressive effect of bronchoalveolar mesenchymal stem cells in hypersensitivity pneumonitis

T2 - Preliminary findings

AU - Balogh, Eniko a.

AU - Nagy, B.

AU - Gyetvai, Ágnes

AU - Bene, Zsolt

AU - Hendrik, Zoltán

AU - Jeney, Viktória

AU - Nagy, Péter

AU - Papp, Ágnes

AU - Balla, J.

AU - Balla, György

AU - Kappelmayer, János

AU - Nagy, Béla

PY - 2016

Y1 - 2016

N2 - Background: 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. Methods: 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. Results: 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. Conclusions: 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.

AB - Background: 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. Methods: 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. Results: 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. Conclusions: 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.

KW - Bronchoalveolar lavage

KW - Hypersensitivity pneumonitis

KW - Mesenchymal stem cells

KW - T-lymphocyte proliferation and activation

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