title: Bronchoalveolar lavage fluid IFN-γ+ Th17 cells and regulatory T cells in pulmonary sarcoidosis.
abstract: In sarcoidosis, increased Th17 cell fractions have been reported in bronchoalveolar lavage fluid, and elevated numbers of Th17 cells producing IFN- γ have been observed in peripheral blood. The balance between Th1, Th17, and FoxP3(+) CD4(+) T cell subsets in sarcoidosis remains unclear. Bronchoalveolar lavage fluid cells, from 30 patients with sarcoidosis, 18 patients with other diffuse parenchymal lung diseases, and 15 healthy controls, were investigated with flow cytometry for intracellular expression of FoxP3. In a subset of the patients, expression of the cytokines IL17A and IFN- γ was investigated. The fractions of FoxP3(+) CD4(+) T cells and Th17 cells were both lower in sarcoidosis compared to controls (P = 0.017 and P = 0.011, resp.). The proportion of Th17 cells positive for IFN- γ was greater in sarcoidosis than controls (median 72.4% versus 31%, P = 0.0005) and increased with radiologic stage (N = 23, rho = 0.45, and P = 0.03). IFN- γ (+) Th17 cells were highly correlated with Th1 cells (N = 23, rho = 0.64, and P = 0.001), and the ratio of IFN- γ (+) Th17/FoxP3(+) CD4(+) T cells was prominently increased in sarcoidosis. IFN- γ (+) Th17 cells may represent a pathogenic subset of Th17 cells, yet their expression of IFN- γ could be a consequence of a Th1-polarized cytokine milieu. Our results indicate a possible immune cell imbalance in sarcoidosis.
authors.affiliation: Department of Thoracic Medicine, St. Olavs University Hospital, Postboks 3250 Sluppen, 7006 Trondheim, Norway ; Department of Immunology and Transfusion Medicine, St. Olavs University Hospital, 7006 Trondheim, Norway ; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7489 Trondheim, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Tøndell
authors.affiliation: Department of Immunology and Transfusion Medicine, St. Olavs University Hospital, 7006 Trondheim, Norway ; Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, 7489 Trondheim, Norway.
authors.forename: Torolf
authors.initials: T
authors.lastname: Moen
authors.affiliation: Department of Immunology and Transfusion Medicine, St. Olavs University Hospital, 7006 Trondheim, Norway ; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7489 Trondheim, Norway.
authors.forename: Magne
authors.initials: M
authors.lastname: Børset
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7489 Trondheim, Norway.
authors.forename: Øyvind
authors.initials: Ø
authors.lastname: Salvesen
authors.affiliation: Department of Immunology and Transfusion Medicine, St. Olavs University Hospital, 7006 Trondheim, Norway ; Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, 7489 Trondheim, Norway.
authors.forename: Anne Dorthea
authors.initials: AD
authors.lastname: Rø
authors.affiliation: Department of Thoracic Medicine, St. Olavs University Hospital, Postboks 3250 Sluppen, 7006 Trondheim, Norway ; Department of Circulation and Imaging, Norwegian University of Science and Technology, 7489 Trondheim, Norway.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Sue-Chu
mesh_terms: D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D008171:Lung Diseases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012507:Sarcoidosis / Q000276:immunology; D017565:Sarcoidosis, Pulmonary / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D018417:Th1 Cells / Q000166:cytology; D058504:Th17 Cells / Q000166:cytology*
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007371:Interferon-gamma