{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:05:31Z","timestamp":1790517931794,"version":"4.1.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"21","license":[{"start":{"date-parts":[[2000,11,1]],"date-time":"2000-11-01T00:00:00Z","timestamp":973036800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2000,11,1]],"date-time":"2000-11-01T00:00:00Z","timestamp":973036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Gene Ther"],"published-print":{"date-parts":[[2000,11,1]]},"DOI":"10.1038\/sj.gt.3301309","type":"journal-article","created":{"date-parts":[[2002,9,4]],"date-time":"2002-09-04T16:53:55Z","timestamp":1031158435000},"page":"1840-1846","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Immunotherapy of spontaneous type 1 diabetes in nonobese diabetic mice by systemic interleukin-4 treatment employing adenovirus vector-mediated gene transfer"],"prefix":"10.1038","volume":"7","author":[{"given":"M J","family":"Cameron","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G A","family":"Arreaza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Waldhauser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Gauldie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T L","family":"Delovitch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2000,11,6]]},"reference":[{"key":"BF3301309_CR1","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/S1074-7613(00)80392-1","volume":"7","author":"TL Delovitch","year":"1997","unstructured":"Delovitch TL, Singh B . The nonobese diabetic mouse as a model of autoimmune diabetes: immune dysregulation gets the NOD Immunity 1997 7: 727\u2013738","journal-title":"Immunity"},{"key":"BF3301309_CR2","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1006\/jaut.1993.1025","volume":"6","author":"NN Shehadeh","year":"1993","unstructured":"Shehadeh NN, LaRosa F, Lafferty KJ . Altered cytokine activity in adjuvant inhibition of autoimmune diabetes J Autoimmun 1993 6: 291\u2013300","journal-title":"J Autoimmun"},{"key":"BF3301309_CR3","doi-asserted-by":"crossref","first-page":"4874","DOI":"10.4049\/jimmunol.154.9.4874","volume":"154","author":"A Rabinovitch","year":"1995","unstructured":"Rabinovitch A et al. IFN-\u03b3 gene expression in pancreatic islet-infiltrating mononuclear cells correlates with autoimmune diabetes in nonobese diabetic mice J Immunol 1995 154: 4874\u20134882","journal-title":"J Immunol"},{"key":"BF3301309_CR4","doi-asserted-by":"publisher","first-page":"2243","DOI":"10.1172\/JCI119762","volume":"100","author":"GA Arreaza","year":"1997","unstructured":"Arreaza GA et al. Neonatal activation of CD28 signalingovercomes T cell anergy and prevents autoimmune diabetes by an IL-4-dependent mechanism J Clin Invest 1997 100: 2243\u20132253","journal-title":"J Clin Invest"},{"key":"BF3301309_CR5","doi-asserted-by":"crossref","first-page":"4686","DOI":"10.4049\/jimmunol.159.10.4686","volume":"159","author":"MJ Cameron","year":"1997","unstructured":"Cameron MJ et al. IL-4 prevents insulitis and insulin-dependent diabetes mellitus in nonobese diabetic mice by potentiation of regulatory T helper-2 cell function J Immunol 1997 159: 4686\u20134692","journal-title":"J Immunol"},{"key":"BF3301309_CR6","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.4049\/jimmunol.163.3.1696","volume":"163","author":"WS Gallichan","year":"1999","unstructured":"Gallichan WS, Balasa B, Davies JD, Sarvetnick N . Pancreatic IL-4 expression results in islet-reactive Th2 cells that inhibit diabetogenic lymphocytes in the nonobese diabetic mouse J Immunol 1999 163: 1696\u20131703","journal-title":"J Immunol"},{"key":"BF3301309_CR7","doi-asserted-by":"publisher","first-page":"331","DOI":"10.2337\/diabetes.47.3.331","volume":"47","author":"CJ Fox","year":"1998","unstructured":"Fox CJ, Danska JS . Independent genetic regulation of T-cell and antigen-presenting cell participation in autoimmune islet inflammation Diabetes 1998 47: 331\u2013338","journal-title":"Diabetes"},{"key":"BF3301309_CR8","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1006\/cyto.1995.0097","volume":"7","author":"B Pilstrom","year":"1995","unstructured":"Pilstrom B, Bjork L, Bohme J . Demonstration of a Th1 cytokine profile in the late phase of NOD insulitis Cytokine 1995 7: 806\u2013814","journal-title":"Cytokine"},{"key":"BF3301309_CR9","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1084\/jem.178.1.87","volume":"178","author":"MJ Rapoport","year":"1993","unstructured":"Rapoport MJ et al. Interleukin 4 reverses T cell proliferative unresponsiveness and prevents the onset of diabetes in nonobese diabetic mice J Exp Med 1993 178: 87\u201399","journal-title":"J Exp Med"},{"key":"BF3301309_CR10","doi-asserted-by":"publisher","first-page":"667","DOI":"10.2165\/00003495-199448050-00002","volume":"48","author":"WE Aulitzky","year":"1994","unstructured":"Aulitzky WE, Schuler M, Peschel C, Huber C . Interleukins. Clinical pharmacology and therapeutic use Drugs 1994 48: 667\u2013677","journal-title":"Drugs"},{"key":"BF3301309_CR11","doi-asserted-by":"publisher","first-page":"2107","DOI":"10.2337\/diabetes.48.11.2107","volume":"48","author":"N Giannoukakis","year":"1999","unstructured":"Giannoukakis N, Rudert WA, Robbins PD, Trucco M . Targeting autoimmune diabetes with gene therapy Diabetes 1999 48: 2107\u20132121","journal-title":"Diabetes"},{"key":"BF3301309_CR12","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1385\/0-89603-178-0:109","volume-title":"Methods in Molecular Biology. Gene Transfer and Expression Protocols","author":"FL Graham","year":"1991","unstructured":"Graham FL, Prevec L . Manipulation of adenovirus vectors. In: Murray EJ, Walker JM (eds) Methods in Molecular Biology. Gene Transfer and Expression Protocols Humana Press: Clifton, NJ 1991 pp 109\u2013127"},{"key":"BF3301309_CR13","doi-asserted-by":"crossref","first-page":"4615","DOI":"10.4049\/jimmunol.160.9.4615","volume":"160","author":"E Parks","year":"1998","unstructured":"Parks E et al. Transient gene transfer of IL-12 regulates chemokine expression and disease severity in experimental arthritis J Immunol 1998 160: 4615\u20134619","journal-title":"J Immunol"},{"key":"BF3301309_CR14","doi-asserted-by":"publisher","first-page":"2766","DOI":"10.1172\/JCI119823","volume":"100","author":"CM Hogaboam","year":"1997","unstructured":"Hogaboam CM et al. Therapeutic effects of interleukin-4 gene transfer in experimental inflammatory bowel disease J Clin Invest 1997 100: 2766\u20132776","journal-title":"J Clin Invest"},{"key":"BF3301309_CR15","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.1172\/JCI2675","volume":"102","author":"H Yasuda","year":"1998","unstructured":"Yasuda H et al. Local expression of immunoregulatory IL-12p40 gene prolonged syngeneic islet graft survival in diabetic NOD mice J Clin Invest 1998 102: 1807\u20131814","journal-title":"J Clin Invest"},{"key":"BF3301309_CR16","doi-asserted-by":"publisher","first-page":"1730","DOI":"10.2337\/diabetes.48.9.1730","volume":"48","author":"N Giannoukakis","year":"1999","unstructured":"Giannoukakis N et al. Adenoviral gene transfer of the interleukin-1 receptor antagonist protein to human islets prevents IL-1\u03b2-induced beta-cell impairment and activation of islet cell apoptosis in vitro Diabetes 1999 48: 1730\u20131736","journal-title":"Diabetes"},{"key":"BF3301309_CR17","first-page":"1","volume":"99","author":"JJ Ryan","year":"1997","unstructured":"Ryan JJ . Interleukin-4 and its receptor: essential mediators of the allergic response J Allergy Clin Immunol 1997 99: 1\u20135","journal-title":"J Allergy Clin Immunol"},{"key":"BF3301309_CR18","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/1074-7613(94)90044-2","volume":"1","author":"SL Swain","year":"1994","unstructured":"Swain SL . Generation and in vivo persistence of polarized Th1 and Th2 memory cells Immunity 1994 1: 543\u2013552","journal-title":"Immunity"},{"key":"BF3301309_CR19","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1096\/fasebj.11.8.9240963","volume":"11","author":"P Yeh","year":"1997","unstructured":"Yeh P, Perricaudet M . Advances in adenoviral vectors: from genetic engineering to their biology FASEB J 1997 11: 615\u2013623","journal-title":"FASEB J"},{"key":"BF3301309_CR20","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1038\/sj.gt.3300995","volume":"6","author":"R Parks","year":"1999","unstructured":"Parks R, Evelegh C, Graham F . Use of helper-dependent adenoviral vectors of alternative serotypes permits repeat vector administration Gene Therapy 1999 6: 1565\u20131573","journal-title":"Gene Therapy"},{"key":"BF3301309_CR21","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1038\/nm0397-306","volume":"3","author":"KJ Fisher","year":"1997","unstructured":"Fisher KJ et al. Recombinant adeno-associated virus for muscle directed gene therapy Nature Med 1997 3: 306\u2013312","journal-title":"Nature Med"},{"key":"BF3301309_CR22","doi-asserted-by":"publisher","first-page":"2717","DOI":"10.1089\/hum.1998.9.18-2717","volume":"9","author":"WS Gallichan","year":"1998","unstructured":"Gallichan WS et al. Lentivirus-mediated transduction of islet grafts with interleukin 4 results in sustained gene expression and protection from insulitis Hum Gene Ther 1998 9: 2717\u20132726","journal-title":"Hum Gene Ther"},{"key":"BF3301309_CR23","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/71545","volume":"6","author":"T Hollon","year":"2000","unstructured":"Hollon T . Researchers and regulators reflect on first gene therapy death Nature Med 2000 6: 6","journal-title":"Nature Med"},{"key":"BF3301309_CR24","first-page":"1253","volume":"7","author":"CL Addison","year":"1995","unstructured":"Addison CL, Gauldie J, Muller WJ, Graham FL . An adenoviral vector expressing interleukin-4 modulates tumorigenicity and induces regression in a murine breast cancer model Int J Oncol 1995 7: 1253\u20131260","journal-title":"Int J Oncol"},{"key":"BF3301309_CR25","doi-asserted-by":"publisher","first-page":"8802","DOI":"10.1073\/pnas.91.19.8802","volume":"19","author":"AJ Bett","year":"1994","unstructured":"Bett AJ, Haddara W, Prevec L, Aham FL . An efficient and flexible system for construction of adenovirus vectors with insertions or deletions in early regions 1 and 3 Proc Natl Acad Sci USA 1994 19: 8802\u20138806","journal-title":"Proc Natl Acad Sci USA"},{"key":"BF3301309_CR26","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1084\/jem.177.6.1551","volume":"177","author":"NW Lukacs","year":"1993","unstructured":"Lukacs NW et al. The role of macrophage inflammatory protein 1\u03b1 in Schistosoma mansoni egg-induced granulomatous inflammation J Exp Med 1993 177: 1551\u20131559","journal-title":"J Exp Med"}],"container-title":["Gene Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/3301309.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/3301309","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/3301309.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T00:16:58Z","timestamp":1682036218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/3301309"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,11,1]]},"references-count":26,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2000,11,1]]}},"alternative-id":["BF3301309"],"URL":"https:\/\/doi.org\/10.1038\/sj.gt.3301309","relation":{},"ISSN":["0969-7128","1476-5462"],"issn-type":[{"value":"0969-7128","type":"print"},{"value":"1476-5462","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,11,1]]},"assertion":[{"value":"27 March 2000","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2000","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 November 2000","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}