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.
The phenotypic distribution and functional profile of tuberculin-specific CD4 T-cells characterizes different stages of TB infection†
Article first published online: 7 SEP 2012
Copyright © 2012 International Clinical Cytometry Society
Cytometry Part B: Clinical Cytometry
Volume 82B, Issue 6, pages 360–368, November 2012
How to Cite
Streitz, M., Fuhrmann, S., Thomas, D., Cheek, E., Nomura, L., Maecker, H., Martus, P., Aghaeepour, N., Brinkman, R. R., Volk, H.-D. and Kern, F. (2012), The phenotypic distribution and functional profile of tuberculin-specific CD4 T-cells characterizes different stages of TB infection. Cytometry, 82B: 360–368. doi: 10.1002/cyto.b.21041
- Issue published online: 22 OCT 2012
- Article first published online: 7 SEP 2012
- Manuscript Accepted: 31 JUL 2012
- Manuscript Revised: 3 JUL 2012
- Manuscript Received: 11 FEB 2012
- NIH. Grant Number: 1R01EB008400
- Charite – Universitätsmedizin Berlin and Brighton and Sussex Medical School, the Michael Smith Foundation for Health Research
- The Terry Fox Research Institute
- The Terry Fox Foundation, a UBC4YF scholarship
- clinically active tuberculosis;
- latent tuberculosis infection;
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.
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.
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).
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