Figure 1.

Mechanisms of immune suppression by Treg. (A) Treg can suppress their target cells through direct cell-cell interaction. CTLA4/B7 interaction between Treg and dendritic cells can induce IDO production by dendritic cells, and the overall effect of reduction in tryptophan suppresses the proliferation of effector T cells. LAG3/MHCII interaction between Treg and dendritic cells suppresses dendritic cell maturation. CD4⁺ effector T cells are suppressed by the HVEM/BTLA and CTLA4/B7 interaction with Treg. (B) Treg also demonstrates paracrine signalling to suppress its targets. IL-10 is shown to suppress the infiltration of neutrophils in the kidney after ischaemic-reperfusion injury. IL-10 can also induce the conversion from M1 macrophages to M2 macrophages. TGF-β1 is also demonstrated to suppress the differentiation of Th1 cells and prevent the development of colitis. IL-35 can suppress the proliferation of CD4⁺ effector T cells. (C) Another mechanism is metabolic disruption. High affinity IL-2 receptors expressed by Treg depletes IL-2, and this suppresses the activation of CD8⁺ T cells, CD4⁺ T cells and NK cells. The ectoenzymes CD39 and CD73 expressed on Treg cell surface catalyse the conversion of ATP to adenosine. Increased adenosine levels inhibit the proliferation and cytokine release by activated CD4⁺ effector T cells. The overall effect of reduction of ATP leads to reduced maturation of dendritic cells and reduced release of pro-inflammatory IL-1β by monocytes. (D) Treg can induce apoptosis on immune mediators through granzyme/ perforin pathway, and they include monocytes, dendritic cells, NK cells, CD4⁺ and CD8⁺ T cells.