University of Sussex
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Loss of receptor on tuberculin-reactive T-cells marks active pulmonary tuberculosis

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posted on 2023-06-08, 12:40 authored by M Streitz, L Tesfa, V Yildirim, A Yahyazadeh, T Ulrichs, R Lenkei, A Quassem, G Liebetrau, L Nomura, H Maecker, H D Volk, Florian KernFlorian Kern
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

PLoS ONE

ISSN

1932-6203

Publisher

Public Library of Science

Issue

8

Volume

2

Article number

e735

Department affiliated with

  • Clinical and Experimental Medicine Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2012-10-29

First Open Access (FOA) Date

2016-03-22

First Compliant Deposit (FCD) Date

2016-08-17