Figure 1: Mechanisms of Treg mediated suppression. Primary Treg suppression mechanisms include (1) acting as sink for IL-2 due to constitutive high expression of IL-2R and consequently depriving effector T cells of the crucial cytokine [121]; (2) secretion of immune-suppressive cytokines IL-10, TGFβ and IL-35 [122,123]; (3) Granzyme-B dependent killing of target cells [124]; (4) inhibitory signalling through binding of CTLA-4 on Tregs and CD80/86 on DCs and reverse signalling via this interaction leading to elevated levels of IDO in DCs which eventually deplete tryptophan and starve effector T cells [125, 126]; (5) binding of LAG3 to MHC-II molecules on DCs causing reduction in Ag presentation [127]; (6) suppression due to interaction of PD-1 on Tregs and PD-L1 on target cells [61, 100]; (7) extracellular adenosine generated from ATP in concert by cell surface CD39 and CD73 (ecto-5’-nucleotidase) interacts with A2AR on effector T cells and suppresses their function by increasing cAMP levels [128, 129]; (8) chemokines CCL3 and CCL4 secreted by Tregs bind to CCR5 on effector cells triggering their migration and subsequent suppression [61, 101].