Regulatory T (T reg) cells that cozy up to other T cells send inhibitory molecules through cell–cell gap junctions, according to a new study by Bopp et al. (page 1303).
Some thymus-born natural T reg cells need little more than direct contact with their T cell victims to suppress their immune functions. But the mechanism or molecule that controls this contact-dependent inhibition has not yet been found.
One known potent immune suppressor is the intracellular second messenger cyclic adenosine monophophate (cAMP), which blocks T cell proliferation. cAMP levels are low in resting T cells and only marginally increase after activation. T reg cells, however, have constantly high levels of cAMP.
The team now shows that T reg cells use their abundant cAMP to flood conventional T cells and thereby shut them down. The cAMP transfer occurred through gap junctions, which formed upon contact between a T reg cell and an activated T cell. The subsequent increase in cAMP shut down T cell proliferation. cAMP transfer into activated T cells failed when gap junction formation was disrupted.
Together with Deaglio et al. (page 1257; and see “Regulatory cells get new ID” JEM 204:1241), these studies confirm that T reg cells use cAMP and the adenosine-generating pathway to rein in immune activation.