The phenotypic distribution and functional profile of tuberculin-specific CD4 T-cells characterizes different stages of TB infection

Authors

  • Mathias Streitz,

    1. Institut für Medizinische Immunologie der Charité, Campus Mitte, Charité – Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany
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    • Mathias Streitz and Stephan Fuhrmann contributed equally to this work.

  • Stephan Fuhrmann,

    1. Brighton and Sussex Medical School, Falmer, Brighton, BN1 9PX, United Kingdom
    2. Helios Klinikum Berlin-Buch, Schwanebecker Chaussee 50, 13125 Berlin, Germany
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    • Streitz M, Fuhrmann S, Thomas D, Cheek E, Nomura L, Maecker H, Martus P, Aghaeepour N, Brinkman RR, Volk H-D, Kern F. The phenotypic distribution and functional profile of tuberculin-specific CD4 T-cells characterizes different stages of TB infection. Cytometry Part B 2012; 82B: 360–368.

  • David Thomas,

    1. Brighton and Sussex Medical School, Falmer, Brighton, BN1 9PX, United Kingdom
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  • Elizabeth Cheek,

    1. School of Computing, Mathematical and Information Science, University of Brighton, Brighton, BN2 4GJ, United Kingdom
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  • Laurel Nomura,

    1. BD Biosciences, 2350 Qume Drive, San Jose, California 95131
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  • Holden Maecker,

    1. Human Immune Monitoring Center, Fairchild Science Bldg, D039, 299 Campus Dr, Stanford, California 94305
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  • Peter Martus,

    1. Institut fuer Biometrie und Klinische Epidemiologie der Charite, Charité – Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, 10117 Berlin
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  • Nima Aghaeepour,

    1. Terry Fox Laboratory, BC Cancer Agency, 675 West 10th Avenue, Vancouver BC, Canada V5Z 1L3
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  • Ryan R Brinkman,

    1. Terry Fox Laboratory, BC Cancer Agency, 675 West 10th Avenue, Vancouver BC, Canada V5Z 1L3
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  • Hans-Dieter Volk,

    1. Institut für Medizinische Immunologie der Charité, Campus Mitte, Charité – Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany
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  • Florian Kern

    Corresponding author
    1. Institut für Medizinische Immunologie der Charité, Campus Mitte, Charité – Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany
    2. Brighton and Sussex Medical School, Falmer, Brighton, BN1 9PX, United Kingdom
    • Brighton and Sussex Medical School, Research Building, University of Sussex, Falmer Campus, Brighton, BN1 9PX, United Kingdom
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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

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