{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T21:20:19Z","timestamp":1775596819467,"version":"3.50.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2001,6,1]],"date-time":"2001-06-01T00:00:00Z","timestamp":991353600000},"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":[[2001,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We report here that islet-specific expression of TNF-\u03b1 can play a dual role in autoimmune diabetes, depending on its precise timing in relation to the ongoing autoimmune process. In a transgenic model (rat insulin promoter-lymphocytic choriomeningitis virus) of virally induced diabetes, TNF-\u03b1 enhanced disease incidence when induced through an islet-specific tetracycline-dependent promoter system early during pathogenesis. Blockade of TNF-\u03b1 during this phase prevented diabetes completely, suggesting its pathogenetic importance early in disease development. In contrast, TNF-\u03b1 expression abrogated the autoimmune process when induced late, which was associated with a reduction of autoreactive CD8 lymphocytes in islets and their lytic activities. Thus, the fine-tuned kinetics of an autoreactive process undergo distinct stages that respond in a differential way to the presence of TNF-\u03b1. This observation has importance for understanding the complex role of inflammatory cytokines in autoimmunity.<\/jats:p>","DOI":"10.4049\/jimmunol.166.12.7023","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T23:36:18Z","timestamp":1398036978000},"page":"7023-7032","source":"Crossref","is-referenced-by-count":117,"title":["A Dual Role for TNF-\u03b1 in Type 1 Diabetes: Islet-Specific Expression Abrogates the Ongoing Autoimmune Process When Induced Late but Not Early During Pathogenesis"],"prefix":"10.1093","volume":"166","author":[{"given":"Urs","family":"Christen","sequence":"first","affiliation":[{"name":"Departments of Neuropharmacology and Immunology, The Scripps Research Institute , La Jolla, CA 92037"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"Wolfe","sequence":"additional","affiliation":[{"name":"Departments of Neuropharmacology and Immunology, The Scripps Research Institute , La Jolla, CA 92037"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ursula","family":"Mo\u0308hrle","sequence":"additional","affiliation":[{"name":"Departments of Neuropharmacology and Immunology, The Scripps Research Institute , La Jolla, CA 92037"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna C","family":"Hughes","sequence":"additional","affiliation":[{"name":"Departments of Neuropharmacology and Immunology, The Scripps Research Institute , La Jolla, CA 92037"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evelyn","family":"Rodrigo","sequence":"additional","affiliation":[{"name":"Departments of Neuropharmacology and Immunology, The Scripps Research Institute , La Jolla, CA 92037"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E Allison","family":"Green","sequence":"additional","affiliation":[{"name":"Section of Immunobiology, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard A","family":"Flavell","sequence":"additional","affiliation":[{"name":"Section of Immunobiology, Yale University School of Medicine , New Haven, CT 06520"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias G","family":"von Herrath","sequence":"additional","affiliation":[{"name":"Departments of Neuropharmacology and Immunology, The Scripps Research Institute , La Jolla, CA 92037"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2001,6,15]]},"reference":[{"key":"2025032907375913300_R1","first-page":"1562","volume-title":"J. 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