Latent tuberculosis infection treatment and T-cell responses to Mycobacterium tuberculosis-specific antigens

Am J Respir Crit Care Med. 2007 Feb 1;175(3):282-7. doi: 10.1164/rccm.200608-1109OC. Epub 2006 Nov 2.


Rationale: There is currently no available test for monitoring the effect of treatment of latent tuberculosis infection (LTBI) to indicate cure or predict risk of subsequent progression to disease.

Objective: We used the T-SPOT.TB assay, which measures T-cell interferon-gamma responses to the Mycobacterium tuberculosis-specific peptides early secretory antigenic target 6-kD protein (ESAT-6) and culture filtrate protein 10 (CFP-10), to determine the effect of LTBI treatment on these responses.

Methods: A total of 226 tuberculosis contacts with positive T-SPOT.TB results underwent repeat testing on LTBI treatment completion. The majority (96%) received 6 months of isoniazid. The pre- and post-treatment T-SPOT.TB results were analyzed according to the combined and separate responses to ESAT-6 and CFP-10 antigens.

Results: The T-SPOT.TB reverted to negative in 85 (37.6%) contacts at treatment completion. Treatment had a significant effect on the response to CFP-10 (p < 0.001; reversion rate, 48.6%), but not on the response to ESAT-6 (p = 0.081; reversion rate, 21.6%). The median number of spot-forming cells (SFCs)/2.5 x 10(5) peripheral blood mononuclear cells (PBMCs) pre- and post-treatment was 6 versus 4.5 for ESAT-6 (p = 0.116) and 11 versus 4 for CFP-10 (p < 0.001). There was a significant difference between the change (fall) in the pre- and post-treatment responses to CFP-10 (6 SFCs/2.5 x 10(5) PBMCs) and ESAT-6 (0 SFCs/2.5 x 10(5) PBMCs; p < 0.001). Significantly different age-related T-cell responses to the two antigens were found.

Conclusion: LTBI treatment had a differential effect on T-cell responses to ESAT-6 and CFP-10 as measured by the T-SPOT.TB. The quantitative response to CFP-10 may be a useful LTBI treatment-monitoring tool.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, Bacterial / drug effects*
  • Antigens, Bacterial / immunology
  • Antigens, Bacterial / pharmacology*
  • Bacterial Proteins / immunology
  • Bacterial Proteins / pharmacology*
  • Cohort Studies
  • Female
  • Humans
  • Immunoassay
  • Interferon-gamma / analysis
  • Interferon-gamma / metabolism
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis*
  • Peptides / immunology
  • Peptides / pharmacology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • Treatment Outcome
  • Tuberculosis, Pulmonary / drug therapy*
  • Tuberculosis, Pulmonary / immunology


  • Antigens, Bacterial
  • Bacterial Proteins
  • CFP-10 protein, Mycobacterium tuberculosis
  • ESAT-6 protein, Mycobacterium tuberculosis
  • Peptides
  • Mycobacterium tuberculosis antigens
  • Interferon-gamma