title: Recruitment of Mycobacterium tuberculosis specific CD4+ T cells to the site of infection for diagnosis of active tuberculosis.
abstract: Accurate and early diagnosis of active tuberculosis (TB) is problematic as current diagnostic methods show low sensitivity (acid-fast bacilli smears), are time-consuming (culture of biological samples) or show variable results [Mycobacterium tuberculosis (MTB)-specific PCR].
  
  
  OBJECTIVE
  In the course of infection, MTB-specific T cells clonally expand at the site of infection and may thus be used as diagnostic marker for active disease.
  
  
  METHODS
  In this cohort study, the frequency of MTB-specific, interferon (IFN)-gamma expressing CD4(+) T cells obtained from peripheral blood and the site of disease in 25 patients with suspected TB was assessed (n = 11, bronchoalveolar lavage; n = 7, pleural fluid; n = 1, ascites; n = 1, joint fluid; n = 5, cerebrospinal fluid).
  
  
  RESULTS
  Amongst 15 patients who showed proven active TB infection, a striking increase of MTB-specific T cells was detected at the site of infection compared with peripheral blood (median increase: 28.5-fold, range: 7.25-531 fold; median of IFN-gamma-producing CD4(+) T cells from blood: 0.02%, range: 0-0.52%; median of IFN-gamma-producing CD4(+) T cells from the site of infection: 1.81%, range: 0.29-6.55%, P < 0.001).
  
  
  METHODS
  Recruitment of MTB-specific T cells to the site of infection yielded a sensitivity of 100% and specificity of 90%, irrespective of the compartment affected.
  
  
  CONCLUSIONS
  The accumulation of MTB-specific T cells at the site of infection may prove as useful diagnostic marker for an accurate and rapid diagnosis of active TB.
authors.affiliation: Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria. nemethj@uhbs.ch
authors.forename: J
authors.initials: J
authors.lastname: Nemeth
authors.forename: H-M
authors.initials: HM
authors.lastname: Winkler
authors.forename: R H
authors.initials: RH
authors.lastname: Zwick
authors.forename: R
authors.initials: R
authors.lastname: Rumetshofer
authors.forename: P
authors.initials: P
authors.lastname: Schenk
authors.forename: O C
authors.initials: OC
authors.lastname: Burghuber
authors.forename: W
authors.initials: W
authors.lastname: Graninger
authors.forename: M
authors.initials: M
authors.lastname: Ramharter
authors.forename: S
authors.initials: S
authors.lastname: Winkler
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000032:analysis; D001426:Bacterial Proteins / Q000032:analysis; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D012680:Sensitivity and Specificity; D014376:Tuberculosis / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015415:Biomarkers; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D007371:Interferon-gamma