Table 1.

Regulatory immune cell subsets with a potential role in TB

Cell subset	Suppressive mechanism(s)	Potential detrimental effects in TB disease
natural Treg (nTreg) induced Treg (iTreg)	-Suppressive cytokines -Inhibitory surface molecules -Cell cycle arrest -Apoptosis -IL-2 consumption -AMP-mediated suppression -Decreased APC maturation, antigen presentation and/or co-stimulation. -Granzyme B-mediated killing	Suppress Th1 and Th17 effector cell responses early in the infection, either by mechanisms that target effector T and NK cells or that target different APCs. Migration of Tregs from the periphery and/or expansion at the site of infection may enhance bacterial growth in local lesions. Promotes the induction of Bregs, tolerogenic DCs and Mregs.
Regulatory B cells (Breg)	-Suppressive cytokines -Death receptor-ligands	Accumulation of Breg cells in lymphoid follicle-like structures in close proximity to TB lesions in the lung may counteract Th1, Th17 and macrophage functions and promote the recruitment of Treg and Mreg cells to the site of infection. IL-10 production induces iTregs cells.
Tolerogenic DCs	-Suppressive cytokines -Inhibitory surface molecules -Immunosuppressive enzyme IDO	Inhibits T cell proliferation and effector cell differentiation. May enhance expansion of Tregs at the local site of infection.
Alternatively activated macrophages (M2)	-Suppressive cytokines and chemokines -Inhibitory receptors -Arginase-mediated deposition of collagen. -Immunosuppressive enzyme IDO -Crosstalk with stromal cells	Increased bacterial uptake promotes intracellular growth. Support immune polarization of Th2 responses that counteract Th1 immunity and increase tissue remodeling and repair in the infected lung. Arg-1 counteracts iNOS and result in decreased antimicrobial activity of macrophages. May induce Tregs at the local site of infection.
Regulatory macrophages (Mreg)	-Suppressive cytokines -Inhibitory receptors -iNOS-mediated cytotoxicity -Immunosuppressive enzyme IDO	Delete activated T cells and can suppress T cell proliferation using high levels of IL-10 and local induction of iNOS/NO or IDO. May promote the induction of both nTregs and iTregs. Enhanced suppressive activity in concert with myeloid-derived suppressor cells.