Streitz, M, Tesfa, L, Yildirim, V, Yahyazadeh, A, Ulrichs, T, Lenkei, R, Quassem, A, Liebetrau, G, Nomura, L, Maecker, H, Volk, H D and Kern, F (2007) Loss of receptor on tuberculin-reactive T-cells marks active pulmonary tuberculosis. PLoS ONE, 2 (8). e735. ISSN 1932-6203

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Abstract

BACKGROUND: Tuberculin-specific T-cell responses have low diagnostic specificity in BCG vaccinated populations. While subunit-antigen (e.g. ESAT-6, CFP-10) based tests are useful for diagnosing latent tuberculosis infection, there is no reliable immunological test for active pulmonary tuberculosis. Notably, all existing immunological tuberculosis-tests are based on T-cell response size, whereas the diagnostic potential of T-cell response quality has never been explored. This includes surface marker expression and functionality of mycobacterial antigen specific T-cells. METHODOLOGY/PRINCIPAL FINDINGS: Flow-cytometry was used to examine over-night antigen-stimulated T-cells from tuberculosis patients and controls. Tuberculin and/or the relatively M. tuberculosis specific ESAT-6 protein were used as stimulants. A set of classic surface markers of T-cell naive/memory differentiation was selected and IFN-gamma production was used to identify T-cells recognizing these antigens. The percentage of tuberculin-specific T-helper-cells lacking the surface receptor CD27, a state associated with advanced differentiation, varied considerably between individuals (from less than 5% to more than 95%). Healthy BCG vaccinated individuals had significantly fewer CD27-negative tuberculin-reactive CD4 T-cells than patients with smear and/or culture positive pulmonary tuberculosis, discriminating these groups with high sensitivity and specificity, whereas individuals with latent tuberculosis infection exhibited levels in between. CONCLUSIONS/SIGNIFICANCE: Smear and/or culture positive pulmonary tuberculosis can be diagnosed by a rapid and reliable immunological test based on the distribution of CD27 expression on peripheral blood tuberculin specific T-cells. This test works very well even in a BCG vaccinated population. It is simple and will be of great utility in situations where sputum specimens are difficult to obtain or sputum-smear is negative. It will also help avoid unnecessary hospitalization and patient isolation.

Item Type:	Article
Keywords:	Adolescent Adult Aged Aged, 80 and over *Antigens, CD27/diagnostic use/immunology BCG Vaccine/diagnostic use/immunology Biological Markers/*metabolism Cell Separation Cytokines/immunology Female Flow Cytometry Humans Male Middle Aged Prospective Studies Sensitivity and Specificity Sputum/microbiology T-Lymphocyte Subsets/cytology/*immunology T-Lymphocytes/cytology/*immunology Tuberculin/*immunology *Tuberculosis, Pulmonary/diagnosis/immunology Young Adult
Schools and Departments:	Brighton and Sussex Medical School > Clinical and Experimental Medicine
Subjects:	Q Science > QR Microbiology > QR0180 Immunology
Depositing User:	Florian Kern
Date Deposited:	29 Oct 2012 12:22
Last Modified:	14 Mar 2017 02:08
URI:	http://srodev.sussex.ac.uk/id/eprint/41276

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