cAMP analogs prevent activation-induced apoptosis of T cell hybridomas.
Activation of T cell hybridomas through their TCR leads to secretion of IL-2, inhibition of proliferation, and apoptosis. The identification of various inhibitors that prevent activation-induced T cell death (AICD) has helped identify several essential events in apoptosis. For example, inhibition of AICD by dexamethasone indicates a connection between these two programmed death pathways. In this study, we have investigated the interaction between the cAMP signal transduction pathway and the activation- or glucocorticoid-induced cell death. cAMP induced DNA fragmentation in thymocytes. T cell hybridomas displayed different sensitivity to cAMP. Regardless of its cAMP sensitivity, programmed cell death promoted by anti-CD3 or Ag in hybridoma was prevented by the presence of cAMP analogs. In contrast, cAMP had no effect on glucocorticoid-induced T cell death. The inhibitory effect of cAMP on AICD was unlikely to be due to quenching of T cell activation signals, because cAMP added 1 h after T cell activation could still prevent cell death. In addition, the increased binding of AP-1, NF-AT, and NF-kappa B during T cell activation was not significantly affected by cAMP. The presence of the inhibitory cAMP-mediated signals, together with the glucocorticoid-induced pathway, suggest there are at least two distinct mechanisms regulating AICD in immature lymphocytes.
Lee
M R
MR
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, R.O.C.
Liou
M L
ML
Liou
M L
ML
Yang
Y F
YF
Lai
M Z
MZ
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D016259:Genes, myc; D006825:Hybridomas / Q000187:drug effects*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D014157:Transcription Factors / Q000378:metabolism
D014157:Transcription Factors; D005576:Colforsin; D003994:Bucladesine; D003907:Dexamethasone; D004247:DNA; D000242:Cyclic AMP