title: Antigen-specific multifunctional T-cells in sarcoidosis patients with Lofgren's syndrome.
abstract: Sarcoidosis is a granulomatous disease of unknown aetiology, mainly affecting the lungs. Recently, T-cell responses towards a specific mycobacterial protein, catalase-peroxidase (mKatG), were observed in sarcoidosis patients. Bronchoalveolar lavage (BAL) fluid and peripheral blood were obtained from a total of 23 sarcoidosis patients, of whom 13 had Löfgren's syndrome and lung accumulations of T-cell receptor AV2S3+ T-cells. Using six-colour flow cytometry in combination with intracellular cytokine staining, T-cell subsets were studied with regard to interferon (IFN)-γ, tumour necrosis factor (TNF) and interleukin-2 production, after stimulation with mKatG or Mycobacterium tuberculosis purified protein derivate (PPD). Stimulation with mKatG resulted in higher simultaneous IFN-γ and TNF production, but less single IFN-γ production, from total BAL fluid CD4+ T-cells of Löfgren's syndrome patients, when compared with non-Löfgren's patients. In contrast, PPD stimulation gave rise to largely similar cytokine responses in both patient subgroups. Furthermore, mKatG stimulated higher IFN-γ production in BAL fluid and blood AV2S3+ T-cells than AV2S3- T-cells, whereas the opposite was seen in BAL fluid with PPD stimulation. Our finding that patients with Löfgren's syndrome exhibited a more pronounced multifunctional cytokine profile (simultaneous IFN-γ and TNF production) towards the mycobacterial protein mKatG may help to explain the distinct disease presentation in this patient subgroup.
authors.affiliation: Karolinska Institutet, Dept of Medicine, Lung Research Laboratory, L4: 01, Karolinska University Hospital, Solna, 171 76 Stockholm, Sweden. Maria.Wiken@ki.se
authors.forename: Maria
authors.initials: M
authors.lastname: Wikén
authors.forename: Mahyar
authors.initials: M
authors.lastname: Ostadkarampour
authors.forename: Anders
authors.initials: A
authors.lastname: Eklund
authors.forename: Matthew
authors.initials: M
authors.lastname: Willett
authors.forename: Edward
authors.initials: E
authors.lastname: Chen
authors.forename: David
authors.initials: D
authors.lastname: Moller
authors.forename: Johan
authors.initials: J
authors.lastname: Grunewald
authors.forename: Jan
authors.initials: J
authors.lastname: Wahlström
mesh_terms: D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D012507:Sarcoidosis / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D013577:Syndrome; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma