Regulatory T cells attenuate mycobacterial stasis in alveolar and blood-derived macrophages from patients with tuberculosis

Am J Respir Crit Care Med. 2013 Jun 1;187(11):1249-58. doi: 10.1164/rccm.201210-1934OC.


Rationale: There are hardly any data about the frequency of CD4(+)CD25(+)Foxp3(+) regulatory T cells (T-Regs) in the lungs of patients with active tuberculosis (TB).

Objectives: To obtain data about the frequency of CD4(+)CD25(+)Foxp3(+) T-Regs, and their impact on mycobacterial containment, in the lungs of patients with active TB.

Methods: Patients with pulmonary TB (n = 49) and healthy volunteers with presumed latent TB infection (LTBI; n = 38) donated blood and/or bronchoalveolar lavage (BAL) cells obtained by bronchoscopy. T-cell phenotype (Th1/Th2/Th17/T-Reg) and functional status was evaluated using flow-cytometry and (3)H-thymidine proliferation assays, respectively. H37Rv-infected alveolar and monocyte-derived macrophages were cocultured with autologous T-Regs and purified protein derivative (PPD) preprimed T-Reg-depleted effector cells. Mycobacterial containment was evaluated by counting CFUs.

Measurements and main results: In blood and BAL T-Reg levels were higher in TB versus LTBI (P < 0.04), and in TB the frequency of T-Regs was significantly higher in BAL versus blood (P < 0.001). T-Reg-mediated suppression of T-cell proliferation in blood and BAL was concentration-dependent. Restriction of mycobacterial growth in infected alveolar and monocyte-derived macrophages was significantly diminished, and by up to 50%, when T-Regs were cocultured with PPD-primed CD4(+) effector T cells. The levels of CD8(+) T-Regs (CD8(+)CD25(+)Foxp3(+)), IL-17-producing T-Regs (IL-17(+)CD4(+)CD25(+)Foxp3(+)), and IL-17-producing T cells were similar in BAL-TB versus BAL-LTBI. Within the TB group compartmentalization of responses was prominent (T-Reg, IFN-γ, tumor necrosis factor-α, IL-17, and IL-22 significantly higher in BAL vs. blood).

Conclusions: In patients with TB the alveolar compartment is enriched for CD4(+) T-Regs. Peripheral blood-derived T-Regs decrease the ability of alveolar and monocyte-derived macrophages to restrict the growth of Mycobacterium tuberculosis in the presence of effector cells. Collectively, these data suggest that CD4(+)CD25(+)FoxP3(+) T-Regs subvert antimycobacterial immunity in human TB.

Publication types

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

MeSH terms

  • Antigens, Bacterial / immunology*
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / microbiology
  • Bronchoscopy
  • CD4-Positive T-Lymphocytes / immunology
  • Cells, Cultured
  • Cytokines / metabolism
  • Humans
  • Immunity, Cellular*
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / isolation & purification*
  • T-Lymphocytes, Regulatory / immunology*
  • Tuberculosis, Pulmonary / immunology*
  • Tuberculosis, Pulmonary / metabolism
  • Tuberculosis, Pulmonary / microbiology
  • Tuberculosis, Pulmonary / pathology


  • Antigens, Bacterial
  • Cytokines