{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T21:39:51Z","timestamp":1789940391457,"version":"4.0.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1990,7]]},"abstract":"<jats:p>A state of T-cell activation, reflected by a marked degree of spontaneous proliferation in vitro, exists among patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy\/tropical spastic paraparesis (HAM\/TSP) but not in those with retroviral-induced adult T-cell leukemia (ATL). We wished to define the mechanism by which the immune activation of circulating cells from HAM\/TSP is driven, thus gaining insight into the pathogenesis of this HTLV-I-associated disease. By using a modification of the polymerase chain reaction, we compared the levels of interleukin 2 (IL-2) and IL-2 receptor alpha chain (IL-2R alpha) mRNA expression to the transcription of the HTLV-I transactivator gene, pX, in peripheral blood mononuclear cells of HAM\/TSP and ATL patients as well as seropositive carriers. Up-regulation of IL-2 and IL-2R alpha transcripts was detected in HAM\/TSP and seropositive carriers that paralleled the coordinate mRNA expression of the pX transactivator. In addition, IL-2 and soluble IL-2R alpha serum levels in HAM\/TSP and seropositive carriers were elevated. Despite markedly elevated levels of soluble IL-2R alpha in ATL, transcripts for IL-2 and pX were not demonstrable in the circulating cells. Finally, the marked degree of in vitro spontaneous proliferation present in HAM\/TSP was profoundly inhibited by specific anti-IL-2R or anti-IL-2 blocking antibodies. Collectively, these results suggest that immune activation in HAM\/TSP, in contrast to ATL, is virally driven by the transactivation and coordinate expression of IL-2 and IL-2R alpha. This deregulated autocrine process may contribute to the evolution of inflammatory nervous system damage in HAM\/TSP.<\/jats:p>","DOI":"10.1073\/pnas.87.13.5218","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T07:22:10Z","timestamp":1149060130000},"page":"5218-5222","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":139,"title":["Transactivation of interleukin 2 and its receptor induces immune activation in human T-cell lymphotropic virus type I-associated myelopathy: pathogenic implications and a rationale for immunotherapy."],"prefix":"10.1073","volume":"87","author":[{"given":"C L","family":"Tendler","sequence":"first","affiliation":[{"name":"Metabolism Branche, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S J","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Metabolism Branche, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W A","family":"Blattner","sequence":"additional","affiliation":[{"name":"Metabolism Branche, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Manns","sequence":"additional","affiliation":[{"name":"Metabolism Branche, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Murphy","sequence":"additional","affiliation":[{"name":"Metabolism Branche, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Fleisher","sequence":"additional","affiliation":[{"name":"Metabolism Branche, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Hanchard","sequence":"additional","affiliation":[{"name":"Metabolism Branche, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O","family":"Morgan","sequence":"additional","affiliation":[{"name":"Metabolism Branche, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J D","family":"Burton","sequence":"additional","affiliation":[{"name":"Metabolism Branche, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D L","family":"Nelson","sequence":"additional","affiliation":[{"name":"Metabolism Branche, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1990,7]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.87.13.5218","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T12:58:56Z","timestamp":1649854736000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.87.13.5218"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1990,7]]},"references-count":0,"journal-issue":{"issue":"13","published-print":{"date-parts":[[1990,7]]}},"alternative-id":["10.1073\/pnas.87.13.5218"],"URL":"https:\/\/doi.org\/10.1073\/pnas.87.13.5218","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1990,7]]},"assertion":[{"value":"1990-07-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}