Cytokines regulate membrane adenosine deaminase on human activated lymphocytes

CD26 is a lymphocyte marker that can anchor adenosine deaminase (ADA) on th e T cell surface. We found that ADA is regulated by cytokines on the cell s urface during T cell activation. By means of flow cytometry, immunofluoresc ence, and immunoblotting techniques, we found that interleukin (IL)-2 and I L-12 up-regulate ecto-ADA and CD26 expression. In clear contrast, IL-4 led to down-regulation of lymphocyte surface ADA without modifying the level of CD26. Moreover, neither circulating ADA transcription nor mRNA translation was regulated by cytokines. These results, along with absence of total-ADA modulation, the variable amount of ADA found in purified plasma membranes, and the different effect of Brefeldin A on the surface presence of ADA and CD26 indicated that cytokines regulate the translocation of ADA towards th e cell surface through a mechanism not involving CD26. Ecto-ADA protected a ctivated lymphocytes from the toxic effects of extracellular adenosine. The refore, this cell surface ADA control might constitute part of the fine imm unoregulatory mechanism of adenosine-mediated signaling through purinergic receptors in leukocytes.