PLoS ONE (Jan 2007)

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

DOI
https://doi.org/10.1371/journal.pone.0000735
Journal volume & issue
Vol. 2, no. 8
p. e735

Abstract

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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 naïve/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.