title: Pulmonary immune responses against Aspergillus fumigatus are characterized by high frequencies of IL-17 producing T-cells.
abstract: In healthy individuals and in patients with invasive aspergillosis, Aspergillus-specific T-cells in peripheral blood display mainly a Thelper1 phenotype. Although in other fungal infections Thelper17 immunity is important, it was suggested that in aspergillus infection Thelper17 cells do not play a role or may even be detrimental.
  
  
  
  To compare the cytokine profiles of Aspergillus-specific CD4+ T-cells in peripheral blood and in the lung. To investigate the Thelper phenotype at the primary location of A. fumigatus exposure.
  
  
  
  Lung-derived T-cells and peripheral blood T-cells from COPD-patients were stimulated with overlapping peptides of 6 A. fumigatus proteins. Aspergillus-specific T-cells were identified on the basis of the activation marker CD154 and production of TNFα. In addition, production of the cytokines IFNγ, IL-17, IL-4 and IL-5 by the Aspergillus-specific T-cells was measured.
  
  
  
  The majority of lung-derived Aspergillus-specific T-cells displayed a Thelper17 phenotype, and only low percentages of cells produced IFNγ. In contrast, in the peripheral blood of COPD patients Aspergillus-specific T-cells displayed a Thelper1 phenotype, similar as peripheral blood-derived Aspergillus-specific T-cells from healthy individuals.
  
  
  
  These data demonstrate that in A. fumigatus infection, similar as in other fungal infections, Thelper17 cells may play a more important role in the immune response than was appreciated until now.
authors.affiliation: Department of Hematology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; Department of Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands. Electronic address: h.jolink@lumc.nl.
authors.forename: Hetty
authors.initials: H
authors.lastname: Jolink
authors.affiliation: Department of Hematology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
authors.forename: Renate
authors.initials: R
authors.lastname: de Boer
authors.affiliation: Sanquin Research and Landsteiner Laboratory, 1066 CX Amsterdam, The Netherlands.
authors.forename: Pleun
authors.initials: P
authors.lastname: Hombrink
authors.affiliation: Department of Respiratory Medicine, Academic Medical Centre, 1105 AZ Amsterdam, The Netherlands.
authors.forename: René E
authors.initials: RE
authors.lastname: Jonkers
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
authors.forename: Jaap T
authors.initials: JT
authors.lastname: van Dissel
authors.affiliation: Department of Hematology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
authors.forename: J H Frederik
authors.initials: JH
authors.lastname: Falkenburg
authors.affiliation: Department of Hematology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
authors.forename: Mirjam H M
authors.initials: MH
authors.lastname: Heemskerk
mesh_terms: D000368:Aged; D001232:Aspergillus fumigatus / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology; D055744:Invasive Pulmonary Aspergillosis / Q000276:immunology* / Q000382:microbiology; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D020381:Interleukin-17
keywords: Aspergillus fumigatus; Cytokines; Lung diseases, fungal; T-lymphocytes; Th17 cells