Fig. 6.

The CD39/CD73 pathway modulates regulatory T cell (Treg) activity. The activation of T cell receptor (TCR), expressed on Tregs, induces CD39 activity. This increment of ATP-metabolizing activity is critical for the immunosuppressive activity of Tregs because it facilitates the pericellular generation of adenosine, a substantial component of the immunosuppressive and anti-inflammatory functions of Tregs. The inhibitory action of Treg-derived adenosine can be ascribed to the activation of A_2A receptors expressed on T effector cells, which undergo reduced immune activity. In addition, adenosine generation triggers a self-reinforcing loop of Treg functions because the stimulation of A_2A receptors expressed on these cells elicits their expansion and increases their immunoregulatory activity. (Reproduced from [426], with permission from Elsevier)