Recruitment of Mycobacterium Tuberculosis Specific CD4+ T Cells to the Site of Infection for Diagnosis of Active Tuberculosis

J Intern Med. 2009 Jan;265(1):163-8. doi: 10.1111/j.1365-2796.2008.02012.x. Epub 2008 Sep 10.

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].

Objectives: 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.

Design: 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).

Main outcome measure: 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.

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Antigens, Bacterial / analysis
  • Bacterial Proteins / analysis
  • Biomarkers / analysis
  • Biomarkers / blood
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Female
  • Humans
  • Immunity, Cellular
  • Interferon-gamma / immunology
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology*
  • Sensitivity and Specificity
  • Tuberculosis / blood
  • Tuberculosis / diagnosis*
  • Tuberculosis / immunology
  • Young Adult

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • Biomarkers
  • ESAT-6 protein, Mycobacterium tuberculosis
  • Interferon-gamma