Introduction 1 2 3 + + 4 4 6 7 8 9 10 11 12 11 12 9 13 2 14 15 16 2 17 2 2 Purinergic Signalling CD39 in the immune system 1 18 19 Cd39 CD39 20 21 Cd39 20 Cd39 14 Cd39 Cd39 19 Cd39 22 23 Cd39 20 Cd39 Cd39 Cd39 14 24 25 26 27 Cd39 28 Cd39 28 Cd39 Cd39 Cd39 28 29 Cd39 14 Cd39 30 28 31 32 Cd39 33 36 37 38 CD39 expression by immunosuppressive regulatory T cells 39 33 40 + + + 41 42 Cd39 + + + + + + + + + + + + + + + 43 + + + + + 1 + + + 1 + high + dim + + − + + low low Fig. 1 a + open profiles gray profiles + b + + + - - + - - + + striped bars c + + + - - + - - + striped bars - +  + + + + + + + − 40 + + + − + + + + + + high + + dim + − + + + + + + + + 44 + + + − − + − − + + 1 – + 1 + + 1 + + 1 + + − 42 1 Adenosine as a Treg effector molecule Cd39 2 Fig. 2 + + +  9 10 45 9 10 28 46 47 + + − Cd39 48 49 Cd39 + + − 9 50 3 Fig. 3 a + error bars b + Cd39 filled histograms open histograms left panel c + Cd39 filled histograms open histograms left panel d Cd39 + e Cd39 upper panel lower panel Cd39 f Cd39  + Cd39 3 50 Cd39 Cd39 3 3 Cd39 3 Cd39 Cd39 3 Cd39 3 + + 3 3 3 These data validate the importance of adenosine in directing T cell subset differentiation and support a role for CD39 in orchestrating Treg cell suppressive responses under both in vitro and in vivo conditions. Summation This review summarizes components of extracellular nucleotide-mediated signalling pathway in T cells that are impacted upon largely by CD39, the prototypic member of the E-NTPDase family of ecto-nucleotidases. Modulated, distinct NTPDase expression appears to regulate nucleotide- and nucleoside-mediated signalling in the immune system. As the vasculature uses similar mediators to regulate blood fluidity and hemostasis, expression of CD39 on either endothelial or immune cells might allow for full integration of vascular inflammatory and immune cell reactions at sites of injury. There is a wide field for future investigations of the role of nucleotides, nucleosides and ecto-nucleotidases in immune-mediated diseases. Increasing interest in this field may open up new avenues for investigation and the development of new treatment modalities for a large variety of illnesses, including atherosclerosis and the vascular or immune inflammation seen in transplant-related diseases.