Increased expression of CCL4/MIP-1β in CD8+ cells and CD4+ cells in sarcoidosis

Int J Immunopathol Pharmacol. 2014 Apr-Jun;27(2):185-93. doi: 10.1177/039463201402700205.

Abstract

Sarcoidosis is a granulomatous disease with an increased accumulation of T cells in lungs as a result of on-site proliferation and chemotaxis induced by chemokines. It has already been demonstrated that CCL3-5 levels were increased in BAL fluid of sarcoidosis patients. To analyze the expression of CCL3-5 chemokines by T-cell subtypes (CD4+, CD8+, Th1, Th2, Tc1 or Tc2) in the lungs of sarcoidosis patients, fifteen untreated sarcoidosis patients and eighteen control subjects were enrolled in this study. CD4+ and CD8+ cells were isolated from BAL fluid by positive magnetic selection. The expression of CCL3-5 and other cytokines in CD4+ and CD8+ cells were measured by flow cytometry. The percentage of CD4+ or CD8+ cells expressing CCL4 were significantly higher in sarcoidosis patients (22.3% and 58.1%) compared to those seen in healthy subjects (11.1% and 16.5%, P = 0.04 and P = 0.02, respectively). In addition, the expression of CCL3, CCL4 and CCL5 was significantly elevated in CD8+ cells (8.9%, 58.1% and 2.1%) compared to CD4+ cells (2.1%, 22.3% and 0.7%; P = 0.04, P = 0.009 and P = 0.04, respectively), whereas CCL4 was expressed by significantly more Tc1 than Th1 cells in sarcoidosis patients (P = 0.006). Our study shows the possible role of CD8+ cells and CD4+ cells in recruiting T cells to the site of inflammation in sarcoidosis through the release of CCL4, either alone or together with Th1/Tc1-associated cytokines.

MeSH terms

  • Adult
  • Biomarkers / analysis
  • Bronchoalveolar Lavage Fluid / immunology
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Case-Control Studies
  • Cell Communication
  • Chemokine CCL3 / analysis
  • Chemokine CCL4 / analysis*
  • Chemokine CCL5 / analysis
  • Chemotaxis, Leukocyte
  • Female
  • Flow Cytometry
  • Humans
  • Lung / immunology*
  • Lung / pathology
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Sarcoidosis, Pulmonary / immunology*
  • Sarcoidosis, Pulmonary / pathology
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Up-Regulation

Substances

  • Biomarkers
  • CCL3 protein, human
  • CCL4 protein, human
  • CCL5 protein, human
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5