Cyclic AMP directly inhibits IL-2 receptor expression in human T cells: expression of both p55 and p75 subunits is affected.
Using purified human T lymphocytes stimulated in serum-free media with adhered anti-CD3 + exogenous IL-2, we have shown that elevated [cAMP]i (mimicked by CPT-cAMP or induced by the physiological agonist PGE2) directly inhibits mitogen-induced 1) [3H]thymidine incorporation by PBMC, purified T cells, and isolated CD4+ and CD8+ T cell subpopulations; 2) expression of both high- and low-affinity IL-2 receptors; 3) plasma membrane expression of both p55 and p75 subunits of the IL-2 receptor; and 4) expression of p55 mRNA, but not p75 mRNA. The decrease in p55 mRNA is not due to enhanced mRNA metabolism. We conclude that elevated [cAMP]i, acting directly on T cells, inhibits mitogenesis by decreasing IL-2 receptor expression. We discuss the possible physiological relevance for the multiple stages of T cell activation that are sensitive to elevated [cAMP]i.
Krause
D S
DS
Department of Physiology, University of Pennsylvania, Philadelphia.
Deutsch
C
C
D001665:Binding Sites; D015152:Blotting, Northern; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology*; D003609:Dactinomycin / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D046911:Macromolecular Substances; D008970:Molecular Weight; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
D007376:Interleukin-2; D046911:Macromolecular Substances; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D003609:Dactinomycin; D000242:Cyclic AMP; D015232:Dinoprostone