{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T23:47:53Z","timestamp":1769644073130,"version":"3.49.0"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2009,1,1]],"date-time":"2009-01-01T00:00:00Z","timestamp":1230768000000},"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":[[2009,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In previous studies, the mechanisms of acute liver injury and virus exclusion have been examined using a model wherein HBsAg-specific CTL are injected into HBsAg transgenic (Tg) mice. The importance of the role of TNF-\u03b1 in virus exclusion was shown, but its role in liver injury was unclear. We crossed the TNF-\u03b1 knockout mouse and HBsAg-Tg mouse to establish the HBsAg-Tg\/TNF-\u03b1 KO mouse, and examined the influence of TNF-\u03b1 on liver injury. The severity of liver damage, as determined by serum alanine aminotransferase activity, was \u223c100 times greater in HBsAg-Tg\/TNF-\u03b1+\/+ than in HBsAg-Tg\/TNF-\u03b1\u2212\/\u2212 mice after i.v. administration of 5 \u00d7 106 CTLs. This liver damage reached the peak of its severity within 24\u201348 h, and was restored 7 days later. Histopathological examination showed hepatocellular necrosis and inflammatory cell infiltrate 24 h after the CTL injection in HBsAg-Tg\/TNF-\u03b1+\/+ mice but not in HBsAg-Tg\/TNF-\u03b1\u2212\/\u2212 mice. The liver damage was fatal for all HBsAg-Tg\/TNF-\u03b1+\/+ mice that received 1.5 \u00d7 107 CTLs. In contrast, 1.5 \u00d7 107 CTLs could not kill the HBsAg-Tg\/TNF-\u03b1\u2212\/\u2212 mice. The TNF-\u03b1 production level was enhanced after the CTL injection in not only intrahepatic macrophages but also other types of mononuclear cells from non-HBsAg-Tg\/TNF-\u03b1+\/+ mice. An adoptive transfer examination revealed that severe liver damage occurred in HBsAg-Tg\/TNF-\u03b1\u2212\/\u2212 mice that had received mononuclear cells from TNF-\u03b1+\/+ mice. In conclusion, the present study provides evidence that TNF-\u03b1 produced by intrahepatic non-Ag-specific inflammatory cells is critical in the development of lethal necroinflammatory liver disease.<\/jats:p>","DOI":"10.4049\/jimmunol.182.1.391","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:17:12Z","timestamp":1397848632000},"page":"391-397","source":"Crossref","is-referenced-by-count":31,"title":["Role of TNF-\u03b1 Produced by Nonantigen-Specific Cells in a Fulminant Hepatitis Mouse Model"],"prefix":"10.1093","volume":"182","author":[{"given":"Hiroyasu","family":"Ito","sequence":"first","affiliation":[{"name":"Department of Informative Clinical Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuki","family":"Ando","sequence":"additional","affiliation":[{"name":"Department of Informative Clinical Medicine"},{"name":"Goto Clinic, Ohgaki City , Gifu Prefecture,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Cancer Immunotherapy Center, Nagoya Kyoritsu Hospital , Nakagawa, Nagoya,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuniaki","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Informative Clinical Medicine"},{"name":"Human Health Sciences, Graduate School of Medicine and Faculty of Medicine, Kyoto University , Shogoin, Sakyo, Kyoto,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masao","family":"Takemura","sequence":"additional","affiliation":[{"name":"Department of Informative Clinical Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michio","family":"Imawari","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, Showa University School of Medicine , Shinagawa-ku, Tokyo,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisataka","family":"Moriwaki","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, Gifu University Graduate School of Medicine , Gifu City,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuru","family":"Seishima","sequence":"additional","affiliation":[{"name":"Department of Informative Clinical Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2009,1,1]]},"reference":[{"key":"2026012806241092600_R1","first-page":"68","article-title":"CD8+ T cells mediate viral clearance and disease pathogenesis during acute hepatitis B virus infection.","volume-title":"J. 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