CD3- and CD28-Dependent Induction of PDE7 Required for T Cell Activation

Costimulation of both the CD3 and CD28 receptors is essential for T cell activation. Induction of adenosine 3′,5′-monophosphate (cAMP)–specific phosphodiesterase-7 (PDE7) was found to be a consequence of such costimulation. Increased PDE7 in T cells correlated with decreased cAMP, increased interleukin-2 expression, and increased proliferation. Selectively reducing PDE7 expression with a PDE7 antisense oligonucleotide inhibited T cell proliferation; inhibition was reversed by blocking the cAMP signaling pathways that operate through cAMP-dependent protein kinase (PKA). Thus, PDE7 induction and consequent suppression of PKA activity is required for T cell activation, and inhibition of PDE7 could be an approach to treating T cell–dependent disorders.