Publication Date:
1999-02-05
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, L -- Yee, C -- Beavo, J A -- DK21723/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1999 Feb 5;283(5403):848-51.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Molecular and Cellular Biology Program, Box 357280, University of Washington School of Medicine, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9933169" target="_blank"〉PubMed〈/a〉
Keywords:
3',5'-Cyclic-AMP Phosphodiesterases/*biosynthesis/genetics/metabolism
;
Antibodies
;
Antigens, CD28/immunology/*physiology
;
Antigens, CD3/immunology/*physiology
;
CD4-Positive T-Lymphocytes/enzymology/immunology
;
Cells, Cultured
;
Cyclic AMP/metabolism
;
Cyclic AMP-Dependent Protein Kinases/metabolism
;
Cyclic Nucleotide Phosphodiesterases, Type 7
;
Enzyme Induction
;
Humans
;
Interleukin-2/biosynthesis
;
Isoenzymes/*biosynthesis/genetics/metabolism
;
*Lymphocyte Activation
;
Oligonucleotides, Antisense/pharmacology
;
RNA, Messenger/genetics/metabolism
;
Reverse Transcriptase Polymerase Chain Reaction
;
T-Lymphocytes/*enzymology/*immunology/metabolism
;
Tumor Cells, Cultured
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
