Potential use of an antagonist of cAMP-dependent protein kinase to block inhibition and modulate T-cell receptor-triggered activation of cytotoxic T-lymphocytes.
It was recently established that cAMP-dependent protein kinase (PK-A) inhibits both early and late stages of T-cell receptor-mediated cytotoxic T-lymphocyte (CTL) activation. We suggested that PK-A may function as a part of a biochemical down-regulating "off" signal in regulation of CTL activities. It is proposed here to use antagonists of PK-A to block such an inhibitory pathway, thereby enhancing immune response. We explored this possibility using the diastereomer of adenosine cyclic 3',5'-phosphorothioate (Rp-cAMPS), a recently described PK-A antagonist. It is shown that Rp-cAMPS blocks cAMP-induced inhibition of lytic activity and of exocytosis of granules from CTL. The immunomodulating potential of cAMP analogues which inhibit PK-A is discussed.
Takayama
H
H
Laboratory of Immunology, National Institutes of Health, Bethesda, MD 20892.
Sitkovsky
M V
MV
D000249:Adenosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002860:Chromium Radioisotopes; D005576:Colforsin / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008213:Lymphocyte Activation / Q000187:drug effects; D047428:Protein Kinase Inhibitors; D013601:T-Lymphocytes / Q000187:drug effects*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects*; D013873:Thionucleotides / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D002860:Chromium Radioisotopes; D007202:Indicators and Reagents; D047428:Protein Kinase Inhibitors; D013873:Thionucleotides; C014308:adenosine 5'-phosphorothioate; D005576:Colforsin; D000249:Adenosine Monophosphate