Treg cells use multiple mechanisms to suppress effector T (Teff) cells, including the newly identified process that involves induction of target cell senescence. Treg cells produce inhibitory cytokines (such as TGFβ, IL-10, and IL-35), cytolytic enzymes (such as granzyme A/B), and suppressive molecules (such as cAMP). They also express surface receptors, including CD25 (IL-2R), CD39, CD73, CTLA4, and LAG3, important for immune regulation. Treg cells induce senescence of responder cells by up-regulation of p38 and ERK1/2 activities, and this in turn endows them with suppressive functions, thereby reinforcing Treg-mediated suppression. Stimulation with TLR8 ligands abrogates the ability of Treg cells to induce senescence. Professional illustration by Alice Y. Chen.