{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T16:53:48Z","timestamp":1769878428977,"version":"3.49.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":730,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>There are several murine models described with features similar to human primary biliary cirrhosis (PBC). Among these models, the one which has the closest serologic features to PBC is a mouse with a T-cell-restricted expression of the dominant negative transforming growth factor \u03b2 receptor type II (dnTGF\u03b2RII). Our work has demonstrated that CD8<jats:sup>+<\/jats:sup> T cells from dnTGF\u03b2RII mice transfer autoimmune cholangitis to Rag1<jats:sup>\u2212\/\u2212<\/jats:sup> recipients. However, it remained unclear whether the autoimmune cholangitis was secondary to an intrinsic function within CD8<jats:sup>+<\/jats:sup> T cells or due to the abnormal TGF\u03b2R environment within which CD8<jats:sup>+<\/jats:sup> T cells were generated. To address this mechanistic issue, we used our dnTGF\u03b2RII, OT-I\/Rag1<jats:sup>\u2212\/\u2212<\/jats:sup>, OT-II\/Rag1<jats:sup>\u2212\/\u2212<\/jats:sup> mice and in addition generated OT-I\/dnTGF\u03b2RII\/Rag1<jats:sup>\u2212\/\u2212<\/jats:sup>, and OT-II\/dnTGF\u03b2RII\/Rag1<jats:sup>\u2212\/\u2212<\/jats:sup> mice in which the entire T-cell repertoire was replaced with ovalbumin (OVA)-specific CD8<jats:sup>+<\/jats:sup> or CD4<jats:sup>+<\/jats:sup> T cells, respectively. Importantly, neither the parental OT-I\/dnTGF\u03b2RII\/Rag1<jats:sup>\u2212\/\u2212<\/jats:sup> mice and\/or OT-II\/dnTGF\u03b2RII\/Rag1<jats:sup>\u2212\/\u2212<\/jats:sup> mice developed cholangitis. However, adoptive transfer demonstrated that only transfer of CD8<jats:sup>+<\/jats:sup> T cells from dnTGF\u03b2RII mice but not CD8<jats:sup>+<\/jats:sup> T cells from OT-I\/Rag1<jats:sup>\u2212\/\u2212<\/jats:sup> mice or from OT-I\/dnTGF\u03b2RII\/Rag1<jats:sup>\u2212\/\u2212<\/jats:sup> mice transferred disease. These data were not secondary to an absence of CD4<jats:sup>+<\/jats:sup> T cell help since a combination of CD8<jats:sup>+<\/jats:sup> T cells from OT-I\/dnTGF\u03b2RII\/Rag1<jats:sup>\u2212\/\u2212<\/jats:sup> and CD4<jats:sup>+<\/jats:sup> T cells from OT II\/dnTGF\u03b2RII\/Rag1<jats:sup>\u2212\/\u2212<\/jats:sup> or CD8<jats:sup>+<\/jats:sup> T cells from OT-I\/dnTGF\u03b2RII\/Rag1<jats:sup>\u2212\/\u2212<\/jats:sup> with CD4<jats:sup>+<\/jats:sup> T cells from OT-II\/Rag1<jats:sup>\u2212\/\u2212<\/jats:sup> mice failed to transfer disease. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: Defective TGF\u03b2RII signaling, in addition to clonal CD8<jats:sup>+<\/jats:sup> T cells that target biliary cells, are required for induction of autoimmune cholangitis. (Hepatology 2013;53:1094\u20131104)<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.26418","type":"journal-article","created":{"date-parts":[[2013,3,26]],"date-time":"2013-03-26T17:35:26Z","timestamp":1364319326000},"page":"1094-1104","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":43,"title":["Clonality, Activated Antigen-Specific Cd8+ T Cells, And Development of Autoimmune Cholangitis in Dntgf\u03b2Rii 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