Introduction
Cytokinins are a class of phytohormones that are involved in multiple aspects of plant growth and development.1 Naturally occurring cytokinins are predominantly adenine derivatives, and almost all cytokinins exist in plants as both a free base and corresponding nucleosides and nucleotides. Although cytokinin-binding proteins have been identified in mammalian sera, the biological functions of cytokinins and underlying mechanisms of action in mammalian systems remain largely uncharacterized.2,3,4 Interestingly, the cytokinin zeatin riboside has been shown to activate adenosine A2A receptor signaling in a mammalian neuronal cell line.5 Although the expression of the Gs-coupled A2AR varies widely by mammalian cell type, it is known to be broadly expressed by immune system cells, with the activation of the A2AR playing a role in terminating inflammation via the regulation of cells involved in innate and adaptive immunity.6 Given the adenosine-based structure of zeatin riboside, its activity as an A2AR agonist is not entirely surprising; however, it does endow the compound with significant therapeutic potential. We show for the first time that zeatin riboside modulates mammalian T lymphocyte activity in an A2AR-dependent manner via the inhibition of pro-inflammatory cytokine production and activation marker expression by CD4+ and CD8+ T lymphocytes.