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

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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.

Original languageEnglish
Pages (from-to)475-486
Number of pages12
JournalJournal of Infection
Issue number6
Publication statusPublished - Jun 2013


  • Active tuberculosis
  • CD4
  • Cured tuberculosis
  • Latent tuberculosis
  • M. tuberculosis
  • Memory profile
  • Polyfunctional T-cells
  • Quantiferon
  • RD1
  • Tuberculosis

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases


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