Fig. 1
From: Tipping the balance in autoimmunity: are regulatory t cells the cause, the cure, or both?
Suppressive Mechanisms of Tregs. Tregs-mediated immune regulation occurs by various cell-contact dependent and contact-independent mechanisms. Anti-inflammatory cytokines, such as TGF-β, IL35, and IL-10, modulate conventional T cells and monocytes towards immunotolerant states. Secretion of Perforin and Granzyme directly targets effector cells and induces apoptosis. By contact-dependent interaction via PD-1/PD-1L, MHC-II/TCR and CTLA4/CD80/CD86 Tregs prevent costimulatory signals in conventional T cells and downregulate the expression of MHC-II and CD80/86 on APCs. Similarly, binding of CTLA-4 to CD80/86 on APCs induces the expression of IDO, converts tryptophan to kynurenine and thereby further suppresses the activation of conventional T cells and promotes regulatory the exertion function in various cell types. Characteristically, high expression of CD25 on Tregs enables Tregs to sequester IL-2 from the environment, thereby limiting IL-2-mediated activation of conventional T cells. Metabolic deprivation is further enhanced by the expression of CD39 on Tregs, which converts ATP to AMP, reducing T-cell proliferation. Tregs may further reduce monocyte differentiation toward pro-inflammatory monocytes and promote M2 macrophage development