Possible mechanisms of regulatory T (TR) cell suppression. These mechanisms are not necessarily mutually exclusive, and potentially two or more might act in concert. (a) Antigen-presenting cell (APC)-activated TR cells transduce an unidentified active negative signal to nearby effector T (TE) cells located on the same APC or an adjacent one. (b) TR cells outcompete TE cells for stimulatory ligands on the APC surface by virtue of their high expression of adhesion molecules. (c) TR cells modulate the behaviour of the APC so that they become ineffective or suppressive stimulators of TE cells. (d) CD25 expression by the TR cells acts as an interleukin-2 sink and hinders the autocrine/paracrine stimulation of TE cells.