{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:07:03Z","timestamp":1781104023170,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"19","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1990,10]]},"abstract":"<jats:p>A 10-day course with ART-18, a mouse monoclonal antibody (mAb) directed against the rat interleukin 2 receptor (IL-2R), prolongs the survival of (LEW x BN)F1 cardiac allografts in LEW recipients to approximately 3 weeks (acute rejection = 8 days, P less than 0.001). We examined host responses against ART-18 idiotype (Id) and mouse immunoglobulin in recipients immunomodulated with ART-18 mAb. Treatment with ART-18 elicited high titers of anti-Id antibodies 14 days after transplantation. However, naive rats given ART-18 before transplantation showed strong anti-Id responses as early as day 4 after engraftment, coinciding with abrogation of the treatment effect (graft survival, approximately 10 days). Preimmunization with irrelevant mouse IgG, which elicited high titers of anti-IgG, did not influence the efficacy of ART-18 upon graft survival (17 days). The use of cyclosporin A (CsA) in conjunction with ART-18 prior to transplantation suppressed the anti-Id response and led to dramatic graft prolongation (greater than 58 days), with two of five grafts surviving indefinitely. This striking effect of CsA plus ART-18 pretreatment did not depend upon CsA per se, as grafts were rejected within 12 days in animals pretreated with CsA alone; in both groups CsA trough levels were comparable. Moreover, administration of CsA before transplantation in concert with control IgG (instead of ART-18) prompted rejection within 2-4 weeks. Thus, discrete interaction(s) between anti-IL-2R mAb and CsA prior to engraftment induces partial host unresponsiveness\/tolerance to anti-IL-2R mAb treatment following transplantation and suppresses the neutralizing anti-Id responses, which results in long-term\/permanent graft acceptance. This study provides a strategy to overcome the anti-Id response mounted by graft recipients that otherwise limits the efficacy of anti-IL-2R mAb treatment.<\/jats:p>","DOI":"10.1073\/pnas.87.19.7375","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T07:27:44Z","timestamp":1149060464000},"page":"7375-7379","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":4,"title":["Pretreatment with cyclosporine and anti-interleukin 2 receptor antibody abrogates the anti-idiotype response in rat recipients of cardiac allografts."],"prefix":"10.1073","volume":"87","author":[{"given":"K","family":"Tanaka","sequence":"first","affiliation":[{"name":"Harvard Medical School, Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N L","family":"Tilney","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K G","family":"Stunkel","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W W","family":"Hancock","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Diamantstein","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J W","family":"Kupiec-Weglinski","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1990,10]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.87.19.7375","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:23:04Z","timestamp":1649856184000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.87.19.7375"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1990,10]]},"references-count":0,"journal-issue":{"issue":"19","published-print":{"date-parts":[[1990,10]]}},"alternative-id":["10.1073\/pnas.87.19.7375"],"URL":"https:\/\/doi.org\/10.1073\/pnas.87.19.7375","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1990,10]]},"assertion":[{"value":"1990-10-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}