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 ac tivation. Induction of adenosine 3',5'-monophosphate (cAMP)-specific phosph odiesterase-7 (PDE7) was found to be a consequence of such costimulation. I ncreased PDE7 in T cells correlated with decreased cAMP, increased interleu kin-2 expression, and increased proliferation. Selectively reducing PDE7 ex pression with a PDE7 antisense oligonucleotide inhibited T cell proliferati on; inhibition was reversed by blocking the cAMP signaling pathways that op erate 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 di sorders.