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

Mathias Streitz, Lydia Tesfa, Vedat Yildirim, Ali Yahyazadeh, Timo Ulrichs, Rodica Lenkei, Ali Quassem, Gerd Liebetrau, Laurel Nomura, Holden Maecker, Hans Dieter Volk, Florian Kern

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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 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-γ 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.

Original languageEnglish (US)
Article numbere735
JournalPloS one
Volume2
Issue number8
DOIs
StatePublished - Aug 15 2007
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Streitz, M., Tesfa, L., Yildirim, V., Yahyazadeh, A., Ulrichs, T., Lenkei, R., Quassem, A., Liebetrau, G., Nomura, L., Maecker, H., Volk, H. D., & Kern, F. (2007). Loss of receptor on tuberculin-reactive T-cells marks active pulmonary tuberculosis. PloS one, 2(8), [e735]. https://doi.org/10.1371/journal.pone.0000735