Rapid detection of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells

Am J Respir Crit Care Med. 2001 Mar;163(4):824-8. doi: 10.1164/ajrccm.163.4.2009100.


There is no reliable means of detecting latent M. tuberculosis infection, and even in patients with active tuberculosis, infection is often unconfirmed. We hypothesized that M. tuberculosis antigen-specific T cells might reliably indicate infection. We enumerated peripheral blood-derived interferon gamma (IFN-gamma)-secreting T cells responding to epitopes from ESAT-6, an antigen that is highly specific for M. tuberculosis complex but absent from BCG, in four groups of individuals. Forty-five of 47 patients with bacteriologically confirmed tuberculosis had ESAT-6-specific IFN-gamma-secreting T cells, compared with four of 47 patients with nontuberculous illnesses, indicating that these T cells are an accurate marker of M. tuberculosis infection. This assay thus has a sensitivity of 96% (95% confidence interval [CI] 92-100) for detecting M. tuberculosis infection in this patient population. By comparison, of the 26 patients with tuberculosis who had a diagnostic tuberculin skin test (TST), only 18 (69%) were positive (p = 0.003). In addition, 22 of 26 (85%) TST-positive exposed household contacts had ESAT-6-specific T cells, whereas zero of 26 unexposed BCG-vaccinated subjects responded. This approach enables rapid detection of M. tuberculosis infection in patients with active tuberculosis and in exposed asymptomatic individuals at high risk of latent infection; it also successfully distinguishes between M. tuberculosis infection and BCG vaccination. This capability may facilitate tuberculosis control in nonendemic regions.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, Bacterial / analysis*
  • CD4 Antigens / analysis*
  • CD4 Lymphocyte Count
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes, T-Lymphocyte / analysis*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / isolation & purification*
  • Prospective Studies
  • Reference Values
  • Sensitivity and Specificity
  • Tuberculin Test
  • Tuberculosis / diagnosis*
  • Tuberculosis / immunology


  • Antigens, Bacterial
  • CD4 Antigens
  • Epitopes, T-Lymphocyte