Antigen-specific multifunctional T-cells in sarcoidosis patients with Lofgren's syndrome

Eur Respir J. 2012 Jul;40(1):110-21. doi: 10.1183/09031936.00166110. Epub 2011 Dec 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bronchoalveolar Lavage Fluid / immunology
  • Female
  • Humans
  • Interferon-gamma / biosynthesis*
  • Lung / immunology
  • Lung / pathology
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology*
  • Receptors, Antigen, T-Cell / metabolism*
  • Sarcoidosis / immunology*
  • Sarcoidosis / metabolism
  • Signal Transduction
  • Syndrome
  • T-Lymphocyte Subsets / immunology*
  • Tumor Necrosis Factor-alpha / biosynthesis*

Substances

  • Receptors, Antigen, T-Cell
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma