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Published December 1, 1990 | Published
Journal Article Open

cAMP inhibits induction of interleukin 2 but not of interleukin 4 in T cells

Abstract

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.

Additional Information

© 2014 National Academy of Sciences. Communicated by Ray D. Owen, September 14, 1990 (received for review June 11, 1990). We thank Dr. Ronald Schwartz and Dr. David Parker, who generously provided the A.E7 and CDC-25 lines; our colleagues Pat White and Dan Chen, for allowing us to cite their unpublished data; Dr. Kim Bottomly, for her initial gift of D10.G4.1 cells and for her continuing interest and patience; Cherrie Leighton, for her fine help with the figures; and Cathy Blagg, for her excellent preparation of the manuscript. This work was supported by a grant from the U.S. Public Health Service (CA39605) to E.V.R.

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August 19, 2023
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