molecule expression. 14–17 Furthermore, A 2A R activation limits
the severity and progression of multiple inflammatory patho-
logies, including the T lymphocyte-driven ischemia–reperfusion
injury, graft-versus-host disease and colitis. 18–20 For these rea-
sons, the development and/or discovery of selective A 2A R ago-
nists is of great interest. We show for the first time that the
plant-derived hormone zeatin riboside modulates mammalian
T lymphocyte activity via the activation of the A 2A R. Zeatin
riboside treatment induces the production of cAMP by purified
CD3 1 T lymphocytes, potently inhibits the production of both
TH1 and TH2 cytokines by CD4 1 and CD8 1 T cells and limits
the expression of CD25, CD69 and CD40L. Additionally, zeatin
riboside treatment limits thioglycollate-induced peritoneal leu-
kocytosis. The A 2A R-mediated immunomodulatory activities of
zeatin riboside observed in these in vitro and in vivo models are
significant because they suggest that zeatin riboside may have
immunosuppressive effects that directly or indirectly modulate
both T cell-mediated and humoral immune responses. It will be
interesting to investigatethe in vivoimmunomodulatory activity
of zeatin riboside, to examine its pharmacological and toxi-
cological profiles and to determine if zeatin riboside proves to
be more efficacious that other A 2A R agonists in the treatment of
acute or chronic inflammatory disorders.