Mycobacterial heat shock protein-induced blood T lymphocytes subsets and cytokine pattern: comparison of sarcoidosis with tuberculosis and healthy controls

Respirology. 2007 May;12(3):346-54. doi: 10.1111/j.1440-1843.2007.01076.x.

Abstract

Background and objective: Sarcoidosis (SA) is a disorder of unknown aetiology. Mycobacterium tuberculosis heat shock proteins (Mtb-hsp) have been considered as causative agents of SA. The role of Mtb-hsp in the immune response in SA has not been investigated.

Methods: Mtb-hsp-stimulated T-cell subsets and Th1/Th2 cytokine patterns in the supernatant from peripheral blood mononuclear cell cultures from 22 SA patients, 20 tuberculosis (TB) patients and 20 healthy volunteers were compared using flow cytometry.

Results: In unstimulated cultures, a significantly higher percentage of CD8(+)alphabeta(+)T-cells were present in SA versus controls. Similarly there was a significantly increased IL-6 and decreased IL-4 level in SA and significantly lower INF-gamma, IL-2, IL-4, IL-10 production in TB versus controls. After Mtb-hsp stimulation, there was a significantly increased TNF-alpha, IL-6, IL-10 and decreased INF-gamma, IL-2, IL-4 production in SA and significantly increased TNF-alpha, IL-6 concentrations in TB versus controls. CD8(+)gammadelta(+)IL-4(+)T-cells were detected significantly less often in Mtb-hsp-induced cultures in SA versus controls. Comparing SA versus TB, CD4(+)gammadelta(+)TCR-cells were significantly increased in Mtb-hsp-induced cultures in TB versus controls and SA. Before stimulation, significantly increased IL-6, IL-10 and decreased IL-4 level in SA versus TB was revealed, whereas Mtb-hsp stimulation caused significantly increased IL-10 and decreased IL-4 concentrations in SA.

Conclusions: After Mtb-hsp stimulation, increased levels of pro-inflammatory cytokines, TNF-alpha and IL-6 were found in sera from SA and TB patients in comparison with healthy controls; SA patients demonstrated the lowest levels of IL-4 and the highest levels of IL-10.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bacterial Proteins / metabolism*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology
  • Case-Control Studies
  • Cells, Cultured
  • Cytokines / metabolism*
  • Female
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Interleukin-10 / metabolism
  • Interleukin-4 / metabolism
  • Interleukin-6 / metabolism
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / metabolism*
  • Sarcoidosis, Pulmonary / metabolism*
  • Sarcoidosis, Pulmonary / pathology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / pathology
  • Tuberculosis, Pulmonary / metabolism*
  • Tuberculosis, Pulmonary / pathology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Bacterial Proteins
  • Cytokines
  • Heat-Shock Proteins
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4