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Science 5 February 1999:
Vol. 283. no. 5403, pp. 848 - 851
DOI: 10.1126/science.283.5403.848
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Reports

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

Linsong Li, 1 Cassian Yee, 2 Joseph A. Beavo 1*

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.

1 Department of Pharmacology and Molecular and Cellular Biology Program, Box 357280, University of Washington School of Medicine, Seattle, WA 98195, USA.
2 Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA.
*   To whom correspondence should be addressed. E-mail: Beavo{at}u.washington.edu

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