IFNγ/TNFα specific-cells and effector memory phenotype associate with active tuberculosis

J Infect. 2013 Jun;66(6):475-86. doi: 10.1016/j.jinf.2013.02.004. Epub 2013 Feb 24.


Objectives: Controversial results were reported on the role of polyfunctional T-cells in tuberculosis (TB). Our aim was to simultaneously characterize the Mycobacterium tuberculosis (Mtb)-specific immune response as cytokine production and memory phenotype by flow cytometry after in vitro stimulation with region of difference 1 ("RD1") recombinant proteins (ESAT-6 and CFP-10) in patients at different TB stage in a low TB endemic country. To assess the specificity of these findings, we evaluated the response to cytomegalovirus (CMV), an unrelated antigen.

Methods: We enrolled subjects with active TB, cured TB, latent TB infection (LTBI). Cytokine and phenotype profiles of T-cells from whole blood stimulated with "RD1" proteins and CMV were characterized by multi-parametric flow cytometry.

Results: Bifunctional IFNγ(+) TNFα(+) CD4(+) T-cells and effector memory phenotype significantly associated with active TB compared to the LTBI group (p = 0.008, at least p ≤ 0.009 respectively) whereas "RD1"-T-cell response in cured TB and LTBI was characterized by a central memory phenotype (at least p ≤ 0.013 and p ≤ 0.004 respectively vs active TB). In contrast, response to CMV antigen was not associated with a TB-specific status.

Conclusion: We identified qualitative associations between Mtb-specific T-cell and TB status in terms of functional capacity and memory status. These immune correlates may be helpful to trace natural history of TB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Bacterial / immunology
  • Antigens, Viral / immunology
  • Bacterial Proteins / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cytomegalovirus / immunology
  • Female
  • Flow Cytometry
  • Humans
  • Immunologic Memory
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism*
  • Male
  • Middle Aged
  • Phenotype
  • Tuberculosis / immunology*
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism*


  • Antigens, Bacterial
  • Antigens, Viral
  • Bacterial Proteins
  • CFP-10 protein, Mycobacterium tuberculosis
  • ESAT-6 protein, Mycobacterium tuberculosis
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma