cAMP inhibits induction of interleukin 2 but not of interleukin 4 in T cells.
In this report, we explore the nature of the inductive stimuli leading to expression of the divergently regulated lymphokines interleukin 2 (IL-2) and interleukin 4 (IL-4). Elevation of cAMP levels blocks IL-2 induction while sparing IL-4 induction. These effects are gene-specific, not cell-specific, and can be observed in the same cells. Transient transfection experiments using murine IL-2 regulatory sequences to drive expression of a reporter gene show at least part of the inhibition to act at the transcriptional level. The possible biological significance of these results is indicated by the observation that representative type 2 helper T-cell lines maintain significantly higher levels of cAMP per cell than a type 1 helper T-cell line. Fresh splenic CD4+ T cells, which preferentially make IL-2, have particularly low levels of cAMP per cell and a low capacity to elevate cAMP in response to forskolin. However, their response to forskolin increases significantly after several days of stimulation. These results suggest a potential link between differential cAMP regulation and the divergence of memory T cells into effector subsets.
Novak
T J
TJ
Division of Biology, California Institute of Technology, Pasadena 91125.
Rothenberg
E V
EV
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D007375:Interleukin-1; D007376:Interleukin-2; D012333:RNA, Messenger; D011994:Recombinant Proteins; D005576:Colforsin; D015847:Interleukin-4; D000001:Calcimycin; D003994:Bucladesine; D000242:Cyclic AMP; D000527:Alprostadil; D013755:Tetradecanoylphorbol Acetate