{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:39:42Z","timestamp":1781109582641,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"16","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1988,8]]},"abstract":"<jats:p>T lymphocytes are stimulated to proliferate in an autocrine\/paracrine manner by the lymphokine interleukin 2 (IL-2). In seeking further insight into the mechanisms by which IL-2 induces progression of T cells through the G1 phase of the cell cycle, studies were performed with agents that increase cellular adenosine 3',5'-cyclic monophosphate (cAMP), a well-known inhibitor of lymphocyte growth. The addition of dibutyryl-cAMP, cholera toxin, forskolin, or 3-isobutyl-1-methylxanthine to an IL-2-dependent murine T-cell line evoked a dose-related suppression of S-phase transition without affecting cellular viability. Moreover, elevation of cAMP levels led to an accumulation of uniformly small cells, suggesting an arrest in early G1. Consistent with these findings, dibutyryl-cAMP inhibited the incorporation of both [3H]-uridine and [3H]thymidine by IL-2-stimulated, synchronized normal human T cells. Furthermore, maximal inhibition occurred during early G1, as indicated by experiments where the addition of dibutyryl-cAMP was delayed with respect to IL-2 stimulation. Quantitative flow cytometric analysis of RNA and DNA content of IL-2-stimulated cells affirmed that increased cAMP inhibits RNA accumulation and S-phase transition. In addition, exposure of IL-2-dependent, asynchronously proliferating normal human T cells to dibutyryl-cAMP resulted in uniform growth arrest in early G1, the point at which cycling T cells accumulate when they are deprived of IL-2. These results indicate that increased cAMP inhibits G1 progression stimulated by IL-2 and provide a rationale for the use of cAMP analogues as pharmacologic probes for the dissection of molecular events occurring during IL-2 signaling and T-cell G1 transit. They also suggest the possibility of therapeutic immunosuppression by a combination of agents that act at different stages of the T-cell cycle.<\/jats:p>","DOI":"10.1073\/pnas.85.16.6072","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T06:40:46Z","timestamp":1149057646000},"page":"6072-6076","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":67,"title":["cAMP antagonizes interleukin 2-promoted T-cell cycle progression at a discrete point in early G1."],"prefix":"10.1073","volume":"85","author":[{"given":"K W","family":"Johnson","sequence":"first","affiliation":[{"name":"Department of Medicine, Dartmouth Medical School, Hanover, NH 03756."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B H","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Dartmouth Medical School, Hanover, NH 03756."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K A","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Medicine, Dartmouth Medical School, Hanover, NH 03756."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1988,8]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.85.16.6072","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:01:21Z","timestamp":1649854881000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.85.16.6072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1988,8]]},"references-count":0,"journal-issue":{"issue":"16","published-print":{"date-parts":[[1988,8]]}},"alternative-id":["10.1073\/pnas.85.16.6072"],"URL":"https:\/\/doi.org\/10.1073\/pnas.85.16.6072","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1988,8]]},"assertion":[{"value":"1988-08-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}