Impaired function of regulatory T-cells in hypersensitivity pneumonitis

Eur Respir J. 2011 Mar;37(3):632-9. doi: 10.1183/09031936.00055210. Epub 2010 Jul 22.

Abstract

Hypersensitivity pneumonitis (HP) is characterised by lung lymphocytosis. Most individuals exposed to HP antigens remain asymptomatic. The mechanisms involved in the impaired immune tolerance leading to HP are unclear. Normally, T-regulatory (Treg)-cells control the immune response. The aim of the present study was to determine whether Treg-cell suppressive function deficiency can explain the uncontrolled inflammation in HP. Bronchoalveolar lavage (BAL) and blood samples were obtained from normal subjects, asymptomatic individuals and HP patients. BAL and blood Treg-cells were isolated. The ability of Treg-cells to suppress T-cell proliferation and the role of interleukin (IL)-17 was verified. BAL and blood Treg-cells from normal subjects suppressed the proliferative response of activated T-cells by 47.1 and 42%, respectively. BAL and blood Treg-cells from asymptomatic subjects had a slightly decreased activity and suppressed proliferation by 29.4 and 31.8%, respectively. BAL and blood Treg-cells from HP patients were totally nonfunctional and unable to suppress proliferation. Low levels of IL-17 were detected in sera and BAL from both normal and asymptomatic individuals, whereas measurable levels were found in patients. Treg-cells may be involved in antigen tolerance in asymptomatic subjects. Defective Treg-cell function, potentially caused by increased IL-17 production, could account for the exacerbated immune response characteristic of HP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alveolitis, Extrinsic Allergic / blood*
  • Alveolitis, Extrinsic Allergic / immunology
  • Alveolitis, Extrinsic Allergic / pathology
  • Bronchoalveolar Lavage
  • CD28 Antigens / biosynthesis
  • CD3 Complex / biosynthesis
  • CD4-Positive T-Lymphocytes / cytology
  • Humans
  • Immune System
  • Inflammation
  • Interleukin-17 / metabolism
  • Interleukin-2 Receptor alpha Subunit / biosynthesis
  • Male
  • Middle Aged
  • T-Lymphocytes, Regulatory / cytology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • CD28 Antigens
  • CD3 Complex
  • Interleukin-17
  • Interleukin-2 Receptor alpha Subunit
  • Tumor Necrosis Factor-alpha