• Patricia L Semple, Anke B Binder, Malika Davids, Alice Maredza, Richard N van Zyl-Smit, and Keertan Dheda.
• Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa.
• Am. J. Respir. Crit. Care Med.. 2013 Jun 1;187(11):1249-58.

RationaleThere 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).ObjectivesTo 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.MethodsPatients 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 ResultsIn 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).ConclusionsIn 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.

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