title: Loss of receptor on tuberculin-reactive T-cells marks active pulmonary tuberculosis.
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.
  
  
  RESULTS
  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
  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.
authors: Institut für Medizinische Immunologie der Charité, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors: Mathias
authors: M
authors: Streitz
authors: Lydia
authors: L
authors: Tesfa
authors: Vedat
authors: V
authors: Yildirim
authors: Ali
authors: A
authors: Yahyazadeh
authors: Timo
authors: T
authors: Ulrichs
authors: Rodica
authors: R
authors: Lenkei
authors: Ali
authors: A
authors: Quassem
authors: Gerd
authors: G
authors: Liebetrau
authors: Laurel
authors: L
authors: Nomura
authors: Holden
authors: H
authors: Maecker
authors: Hans-Dieter
authors: HD
authors: Volk
authors: Florian
authors: F
authors: Kern
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001500:BCG Vaccine / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism*; D002469:Cell Separation; D016207:Cytokines / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D013183:Sputum / Q000382:microbiology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014373:Tuberculin / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology; D055815:Young Adult
chemical_list: D001500:BCG Vaccine; D015415:Biomarkers; D016207:Cytokines; D014373:Tuberculin; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
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