Loss of receptor on tuberculin-reactive T-cells marks active pulmonary tuberculosis.
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.
Streitz
Mathias
M
Institut für Medizinische Immunologie der Charité, Charité Universitätsmedizin Berlin, Berlin, Germany.
Tesfa
Lydia
L
Yildirim
Vedat
V
Yahyazadeh
Ali
A
Ulrichs
Timo
T
Lenkei
Rodica
R
Quassem
Ali
A
Liebetrau
Gerd
G
Nomura
Laurel
L
Maecker
Holden
H
Volk
Hans-Dieter
HD
Kern
Florian
F
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
D001500:BCG Vaccine; D015415:Biomarkers; D016207:Cytokines; D014373:Tuberculin; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
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