title: The phenotypic distribution and functional profile of tuberculin-specific CD4 T-cells characterizes different stages of TB infection.
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.
authors.affiliation: Institut für Medizinische Immunologie der Charité, Campus Mitte, Charité - Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Streitz
authors.forename: Stephan
authors.initials: S
authors.lastname: Fuhrmann
authors.forename: David
authors.initials: D
authors.lastname: Thomas
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cheek
authors.forename: Laurel
authors.initials: L
authors.lastname: Nomura
authors.forename: Holden
authors.initials: H
authors.lastname: Maecker
authors.forename: Peter
authors.initials: P
authors.lastname: Martus
authors.forename: Nima
authors.initials: N
authors.lastname: Aghaeepour
authors.forename: Ryan R
authors.initials: RR
authors.lastname: Brinkman
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Florian
authors.initials: F
authors.lastname: Kern
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand / Q000096:biosynthesis / Q000276:immunology; D002478:Cells, Cultured; D003581:Cytodiagnosis / Q000379:methods; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology; D007376:Interleukin-2 / Q000032:analysis / Q000276:immunology; D055985:Latent Tuberculosis / Q000175:diagnosis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D014373:Tuberculin / Q000494:pharmacology*; D014374:Tuberculin Test; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology; D055815:Young Adult
chemical_list: C508594:IL2 protein, human; D007376:Interleukin-2; D014373:Tuberculin; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D007371:Interferon-gamma