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

Research output: Contribution to journalArticle

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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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tuberculin
T-cells
Tuberculin
Pulmonary Tuberculosis
tuberculosis
T-lymphocytes
lungs
T-Lymphocytes
receptors
Mycobacterium bovis
Latent Tuberculosis
Antigens
Immunologic Tests
antigens
Tuberculosis
Sputum
immunologic techniques
Patient Isolation
diagnostic specificity
Flow cytometry

ASJC Scopus subject areas

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

Cite this

Streitz, M., Tesfa, L., Yildirim, V., Yahyazadeh, A., Ulrichs, T., Lenkei, R., ... 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

Loss of receptor on tuberculin-reactive T-cells marks active pulmonary tuberculosis. / Streitz, Mathias; Tesfa, Lydia; Yildirim, Vedat; Yahyazadeh, Ali; Ulrichs, Timo; Lenkei, Rodica; Quassem, Ali; Liebetrau, Gerd; Nomura, Laurel; Maecker, Holden; Volk, Hans Dieter; Kern, Florian.

In: PLoS One, Vol. 2, No. 8, e735, 15.08.2007.

Research output: Contribution to journalArticle

Streitz, M, Tesfa, L, Yildirim, V, Yahyazadeh, A, Ulrichs, T, Lenkei, R, Quassem, A, Liebetrau, G, Nomura, L, Maecker, H, Volk, HD & Kern, F 2007, 'Loss of receptor on tuberculin-reactive T-cells marks active pulmonary tuberculosis', PLoS One, vol. 2, no. 8, e735. https://doi.org/10.1371/journal.pone.0000735
Streitz, Mathias ; Tesfa, Lydia ; Yildirim, Vedat ; Yahyazadeh, Ali ; Ulrichs, Timo ; Lenkei, Rodica ; Quassem, Ali ; Liebetrau, Gerd ; Nomura, Laurel ; Maecker, Holden ; Volk, Hans Dieter ; Kern, Florian. / Loss of receptor on tuberculin-reactive T-cells marks active pulmonary tuberculosis. In: PLoS One. 2007 ; Vol. 2, No. 8.
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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.",
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