CD3- and CD28-dependent induction of PDE7 required for T cell activation.

Publication Type:

Journal Article

Source:

Science (New York, N.Y.), Volume 283, Issue 5403, p.848-51 (1999)

Keywords:

3',5'-Cyclic-AMP Phosphodiesterases, Antibodies, Antigens, CD28, Antigens, CD3, CD4-Positive T-Lymphocytes, Cells, Cultured, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, Cyclic Nucleotide Phosphodiesterases, Type 7, Enzyme Induction, Humans, Interleukin-2, Isoenzymes, Lymphocyte Activation, Oligonucleotides, Antisense, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, T-Lymphocytes, Tumor Cells, Cultured

Abstract:

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.