{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T22:02:37Z","timestamp":1791151357909,"version":"4.1.0"},"reference-count":56,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,1,3]]},"abstract":"<jats:p>The administration of concanavalin A (Con A) induces a rapid severe injury of hepatocytes in mice. Although the Con A\u2013induced hepatitis is considered to be an experimental model of human autoimmune hepatitis, the precise cellular and molecular mechanisms that induce hepatocyte injury remain unclear. Here, we demonstrate that V\u03b114 NKT cells are required and sufficient for induction of this hepatitis. Moreover, interleukin (IL)-4 produced by Con A\u2013activated V\u03b114 NKT cells is found to play a crucial role in disease development by augmenting the cytotoxic activity of V\u03b114 NKT cells in an autocrine fashion. Indeed, short-term treatment with IL-4 induces an increase in the expression of granzyme B and Fas ligand (L) in V\u03b114 NKT cells. Moreover, V\u03b114 NKT cells from either perforin knock-out mice or FasL-mutant gld\/gld mice fail to induce hepatitis, and hence perforin\u2013granzyme B and FasL appear to be effector molecules in Con A\u2013induced V\u03b114 NKT cell\u2013mediated hepatocyte injury.<\/jats:p>","DOI":"10.1084\/jem.191.1.105","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"105-114","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":318,"title":["Augmentation of V\u03b114 Nkt Cell\u2013Mediated Cytotoxicity by Interleukin 4 in an Autocrine Mechanism Resulting in the Development of Concanavalin a\u2013Induced Hepatitis"],"prefix":"10.1084","volume":"191","author":[{"given":"Yoshikatsu","family":"Kaneko","sequence":"first","affiliation":[{"name":"aFrom CREST (Core Research for Evolutional Science and Technology) and the Department of Molecular Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michishige","family":"Harada","sequence":"additional","affiliation":[{"name":"aFrom CREST (Core Research for Evolutional Science and Technology) and the Department of Molecular Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsu","family":"Kawano","sequence":"additional","affiliation":[{"name":"aFrom CREST (Core Research for Evolutional Science and Technology) and the Department of Molecular Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakatsu","family":"Yamashita","sequence":"additional","affiliation":[{"name":"aFrom CREST (Core Research for Evolutional Science and Technology) and the Department of Molecular Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youichi","family":"Shibata","sequence":"additional","affiliation":[{"name":"aFrom CREST (Core Research for Evolutional Science and Technology) and the Department of Molecular Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumitake","family":"Gejyo","sequence":"additional","affiliation":[{"name":"bDepartment of Internal Medicine, School of Medicine, Niigata University, Niigata 951-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshinori","family":"Nakayama","sequence":"additional","affiliation":[{"name":"aFrom CREST (Core Research for Evolutional Science and Technology) and the Department of Molecular Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"aFrom CREST (Core Research for Evolutional Science and Technology) and the Department of Molecular Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2000,1,3]]},"reference":[{"key":"2023072509061815600_R1","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1084\/jem.180.3.1097","article-title":"An invariant T cell receptor \u03b1 chain is used by a unique subset of major histocompatibility complex class I\u2013specific CD4+ and CD4\u22128\u2212 T cells in mice and humans","volume":"180","author":"Lantz","year":"1994","journal-title":"J. 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