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-bindingproteinshavebeenidentifiedinmammalian
sera, the biological functions of cytokinins and underlying
mechanisms of action in mammalian systems remain largely
uncharacterized. 2–4 Interestingly, the cytokinin zeatin riboside
has been shown to activate adenosine A 2A receptor signaling in
a mammalian neuronal cell line. 5 Although the expression of
theGs-coupledA 2A Rvarieswidelybymammaliancelltype,itis
known to be broadly expressed by immune system cells, with
the activationofthe A 2A Rplayingarole in terminating inflam-
mation via the regulation of cells involved in innate and adap-
tive immunity. 6 Given the adenosine-based structure of zeatin
riboside, its activity as an A 2A R agonist is not entirely surpris-
ing; however, it does endow the compound with significant
therapeutic potential. We show for the first time that zeatinriboside modulates mammalian T lymphocyte activity in an
A 2A R-dependent manner via the inhibition of pro-inflamma-
tory cytokine production and activation marker expression by
CD4 1 and CD8 1 T lymphocytes.