{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T18:26:04Z","timestamp":1770834364240,"version":"3.50.1"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2000,7,1]],"date-time":"2000-07-01T00:00:00Z","timestamp":962409600000},"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":[[2000,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We report the development and characterization of a novel model of severe hepatitis induced against hepatitis B virus surface Ag (HBsAg). HBsAg was successfully targeted into the liver in soluble form. Using this unique property of HBsAg, we established a liver injury model induced by HBsAg-specific Th1 cells. Severe liver injury was induced in C57BL\/6 mice by injection of HBsAg together with HBsAg-specific Th1 cells. Histochemical examination demonstrated extensive necroinflammatory hepatic lesions in these animals. Application of this liver injury model to mutant or gene knockout mice enabled us to define the effector mechanisms of Th1 cells in fulminant hepatitis. When Fas-deficient lpr mice were used as recipients, a similar degree of liver injury was induced as in wild-type mice. Moreover, HBsAg-specific Th1 cells obtained from perforin\u2212\/\u2212 mice could induce severe liver injury in both wild-type and lpr mice. These results indicated that neither Fas ligand nor perforin are essential for Th1-mediated liver injury in this model. Pretreatment with anti-TNF-\u03b1 mAb prevented liver injury, whereas severe liver injury was induced in TNF-\u03b1\u2212\/\u2212 mice. Moreover, IFN-\u03b3 receptor-deficient mice were resistant to Th1-mediated liver injury. Therefore, TNF-\u03b1 and IFN-\u03b3, which were produced by HBsAg-specific Th1 cells during the effector phase, appeared to be indispensable in the pathogenesis of fulminant hepatitis.<\/jats:p>","DOI":"10.4049\/jimmunol.165.2.956","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T23:02:33Z","timestamp":1398121353000},"page":"956-961","source":"Crossref","is-referenced-by-count":50,"title":["Indispensable Role for TNF-\u03b1 and IFN-\u03b3 at the Effector Phase of Liver Injury Mediated by Th1 Cells Specific to Hepatitis B Virus Surface Antigen"],"prefix":"10.1093","volume":"165","author":[{"given":"Akio","family":"Ohta","sequence":"first","affiliation":[{"name":"Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University , Sapporo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Sekimoto","sequence":"additional","affiliation":[{"name":"Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University , Sapporo ,","place":["Japan"]},{"name":"Division of Biological Sciences, Graduate School of Science, Hokkaido University , Sapporo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marimo","family":"Sato","sequence":"additional","affiliation":[{"name":"Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University , Sapporo ,","place":["Japan"]},{"name":"Section of Genetic Engineering, Research Center for Genetic Engineering and Cell Transplantation, Tokai University School of Medicine , Isehara ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiaki","family":"Koda","sequence":"additional","affiliation":[{"name":"Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University , Sapporo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin-ichiro","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences, Graduate School of Science, Hokkaido University , Sapporo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoichiro","family":"Iwakura","sequence":"additional","affiliation":[{"name":"Center for Experimental Medicine, Institute of Medical Science, University of Tokyo , Tokyo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Sekikawa","sequence":"additional","affiliation":[{"name":"Department of Immunology, National Institute of Animal Health , Tsukuba ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University , Sapporo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2000,7,15]]},"reference":[{"key":"2026020213071198900_R1","first-page":"1472","volume-title":"J. 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