{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T16:25:39Z","timestamp":1770740739568,"version":"3.49.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[1990,2,1]],"date-time":"1990-02-01T00:00:00Z","timestamp":633830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1990,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The structurally related immunosuppressive macrolides FK-506 and rapamycin (RAP) were previously shown to inhibit T cell stimulation through different mechanisms. FK-506 acts similarly to cyclosporin A (CsA) and prevents IL-2 production and IL-2R expression. RAP has little or no effect on these events but markedly impedes the response to IL-2. The present study was initiated to examine the possibility of a complementation between the immunosuppressive actions of RAP and FK-506 or CsA on various murine T cell responses. RAP potentiated the effect of CsA on proliferation and IL-2R expression in T cells stimulated with ionomycin + PMA. However, in the same system, RAP acted as a potent antagonist of FK-506 suppression. RAP also blocked FK-506- but not CsA-mediated inhibition of IL-2 mRNA induction. By using model systems sensitive to inhibition by RAP but not FK-506 we further demonstrated that FK-506 reciprocally behaves as an antagonist of RAP. In one such model, the stimulation of splenic T cells with IL-2 + PMA, FK-506, but not CsA, reversed the suppressive effect of RAP on proliferation. FK-506 also antagonized RAP-mediated inhibition with respect to the induction of Ly-6E Ag expression by IFN in YAC cells. To explore further the competition between the two macrolides at the cellular level, we performed binding experiments with a radiolabeled derivative of FK-506. Both FK-506 and RAP, but not CsA, inhibited the binding of this probe in YAC cells. Taken together, these data demonstrate that FK-506 and RAP antagonize each other's biologic activity and physically interact with a common receptor site(s) in T cells. Moreover, CsA acts at a site distinct from the cellular target(s) of FK-506 or RAP.<\/jats:p>","DOI":"10.4049\/jimmunol.144.4.1418","type":"journal-article","created":{"date-parts":[[2022,12,31]],"date-time":"2022-12-31T07:56:54Z","timestamp":1672473414000},"page":"1418-1424","source":"Crossref","is-referenced-by-count":261,"title":["The immunosuppressive macrolides FK-506 and rapamycin act as reciprocal antagonists in murine T cells."],"prefix":"10.1093","volume":"144","author":[{"given":"F J","family":"Dumont","sequence":"first","affiliation":[{"name":"Department of Immunology Research, Merck, Sharp and Dohme Research Laboratories , PO Box 2000, Rahway, NJ 07065"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M R","family":"Melino","sequence":"additional","affiliation":[{"name":"Department of Immunology Research, Merck, Sharp and Dohme Research Laboratories , PO Box 2000, Rahway, NJ 07065"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M J","family":"Staruch","sequence":"additional","affiliation":[{"name":"Department of Immunology Research, Merck, Sharp and Dohme Research Laboratories , PO Box 2000, Rahway, NJ 07065"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S L","family":"Koprak","sequence":"additional","affiliation":[{"name":"Department of Immunology Research, Merck, Sharp and Dohme Research Laboratories , PO Box 2000, Rahway, NJ 07065"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P A","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Immunology Research, Merck, Sharp and Dohme Research Laboratories , PO Box 2000, Rahway, NJ 07065"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N H","family":"Sigal","sequence":"additional","affiliation":[{"name":"Department of Immunology Research, Merck, Sharp and Dohme Research Laboratories , PO Box 2000, Rahway, NJ 07065"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1990,2,15]]},"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/144\/4\/1418\/62781481\/1418.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/144\/4\/1418\/62781481\/1418.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T02:34:56Z","timestamp":1743302096000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/144\/4\/1418\/8075356"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1990,2]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1990,2,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.144.4.1418","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1990,2]]},"published":{"date-parts":[[1990,2]]}}}