Expression of A(2B) adenosine receptors in human lymphocytes: their role in T cell activation

Extracellular adenosine has a key role in the development and function of t he cells of the immune system. Many of the adenosine actions seem to be med iated by specific surface receptors positively coupled to adenylate cyclase : A(2A) and A(2B). Despite the fact that A(2A) receptors (A(2A)Rs) can be e asily studied due to the availability of the specific agonist CGS21680, a p harmacological and physiological characterization of adenosine A(2B) recept ors (A(2B)Rs) in lymphocytes has not been possible due to the lack of suita ble reagents. Here we report the generation and characterization of a polyc lonal antipeptide antibody raised against the third extracellular loop of t he A(2B)R human clone which is useful for immunocytochemical studies. This antibody has permitted the detection of A(2B)R(+) cells in lymphocyte sampl es isolated from human peripheral blood. The pharmacology of cAMP-producing compounds is consistent with the presence of functional A(2B)Rs but not of A(2A) receptors in these human cells. The percentage of A(2B)R-expressing cells was similar in the CD4(+) or CD8(+) T cell subpopulations. Interestin gly activation signals delivered by either phytohemagglutinin or anti-T cel l receptor/CD3 complex antibodies led to a significant increase in both the percentage of cells expressing the receptor and the intensity of the label ing. These receptors are functional since interleukin-2 production in these cells is reduced by NECA but not by R-PIA or CGS21680. These results show that A(2B)R expression is regulated in T cell activation and suggest that t he role of adenosine in lymphocyte deactivation is mediated by A(2B)Rs.