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Keywords:

  • clinically active tuberculosis;
  • latent tuberculosis infection;
  • T-lymphocytes;
  • CD154;
  • CD27

Abstract

Background:

Recent publications have suggested that altered proportions of functional CD4 T-cell subsets correlate with active pulmonary TB. Also, CD27-expression on tuberculin-activated IFN-γ+ CD4 T-cells is known to differ significantly between patients with active pulmonary TB and healthy TB-unexposed BCG vaccinees. Here, we explore links between CD4 T-cell phenotype, multiple functional subsets, and control of TB.

Methods:

We examined ex-vivo overnight tuberculin activated CD4 T-cells in regards to CD27-expression and the activation markers, CD154 upregulation, IFN-γ, TNF-α, IL-2, and degranulation in 44 individuals, including cases of clinically active pulmonary TB, and hospital staff with prolonged TB exposure, some of whom had latent TB.

Results:

Active pulmonary TB generally showed an excess of TNF-α+ subsets over IFN-γ+ subsets, paralleled by decreased CD27 expression on activated IFN-γ+ or CD154+ CD4 T-cells. The single subset distinguishing best between active pulmonary TB and high TB exposure was CD154+/TNF-α+/ IFN-γ-/IL-2-/degranulation- (AUROC 0.90). The ratio between the frequencies of TNF-α+/IFN-γ+ CD4 T-cells was an effective alternative parameter (AUROC 0.87).

Conclusions:

Functional subsets and phenotype of tuberculin induced CD4 T-cells differ between stages of TB infection. Predominance of TNF-α+ CD4 T-cells in active infection suggests an increased effort of the immune system to contain disease. © 2012 International Clinical Cytometry Society