Multifunctional CD4(+) T Cells Correlate With Active Mycobacterium Tuberculosis Infection

Eur J Immunol. 2010 Aug;40(8):2211-20. doi: 10.1002/eji.201040455.


Th1 CD4(+) T cells and their derived cytokines are crucial for protection against Mycobacterium tuberculosis. Using multiparametric flow cytometry, we have evaluated the distribution of seven distinct functional states (IFN-γ/IL-2/TNF-α triple expressors, IFN-γ/IL-2, IFN-γ/TNF-α or TNF-α/IL-2 double expressors or IFN-γ, IL-2 or TNF-α single expressors) of CD4(+) T cells in individuals with latent M. tuberculosis infection (LTBI) and active tuberculosis (TB). We found that triple expressors, while detectable in 85-90%TB patients, were only present in 10-15% of LTBI subjects. On the contrary, LTBI subjects had significantly higher (12- to 15-fold) proportions of IL-2/IFN-γ double and IFN-γ single expressors as compared with the other CD4(+) T-cell subsets. Proportions of the other double or single CD4(+) T-cell expressors did not differ between TB and LTBI subjects. These distinct IFN-γ, IL-2 and TNF-α profiles of M. tuberculosis-specific CD4(+) T cells seem to be associated with live bacterial loads, as indicated by the decrease in frequency of multifunctional T cells in TB-infected patients after completion of anti-mycobacterial therapy. Our results suggest that phenotypic and functional signatures of CD4(+) T cells may serve as immunological correlates of protection and curative host responses, and be a useful tool to monitor the efficacy of anti-mycobacterial therapy.

Publication types

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

MeSH terms

  • Acute Disease
  • Acyltransferases / immunology
  • Adult
  • Antigens, Bacterial / immunology
  • Bacterial Load* / immunology
  • Bacterial Proteins / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / microbiology
  • CD4-Positive T-Lymphocytes / pathology
  • Cell Separation
  • Chronic Disease
  • Cytokines / metabolism*
  • Flow Cytometry
  • Humans
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology*
  • Mycobacterium tuberculosis / pathogenicity
  • Tuberculosis, Pulmonary / diagnosis
  • Tuberculosis, Pulmonary / immunology*


  • Antigens, Bacterial
  • Bacterial Proteins
  • Cytokines
  • ESAT-6 antigen, Mycobacterium leprae
  • Mycobacterium tuberculosis antigens
  • Acyltransferases
  • antigen 85B, Mycobacterium tuberculosis