Increased intracellular cyclic adenosine monophosphate inhibits T lymphocyte-mediated cytolysis by two distinct mechanisms.
Cholera toxin (CT), but not pertussis toxin (PT), treatment of cloned murine CTL inhibited target cell lysis in a dose-dependent fashion. The effects of CT were mimicked by forskolin and cyclic adenosine monophosphate (cAMP) analogues. Inhibition of cytotoxicity by CT and cAMP analogs was mediated in part by attenuation of conjugate formation. Additionally, both CT and cAMP analogs blocked the increase in intracellular Ca2+ induced by stimulation of the TCR complex by mAbs. These findings indicate that cAMP inhibits the activity of CTL by two distinct mechanisms and suggests a role for this second messenger in CTL-mediated cytolysis.
Gray
L S
LS
Department of Pathology, University of Virginia School of Medicine, Charlottesville 22908.
Gnarra
J
J
Hewlett
E L
EL
Engelhard
V H
VH
D000818:Animals; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D003593:Cytoplasm; D003602:Cytotoxicity, Immunologic; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D037342:Pertussis Toxin; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010566:Virulence Factors, Bordetella; D002772:Cholera Toxin; D000242:Cyclic AMP; D037342:Pertussis Toxin