{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T12:58:40Z","timestamp":1793883520190,"version":"4.7.0"},"reference-count":52,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,3,11]],"date-time":"2013-03-11T00:00:00Z","timestamp":1362960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Cooperative Human Tissue Network and National Disease Research Interchange","award":["5U42-RR006042"],"award-info":[{"award-number":["5U42-RR006042"]}]},{"name":"Cooperative Human Tissue Network and National Disease Research Interchange","award":["DK066917"],"award-info":[{"award-number":["DK066917"]}]},{"name":"Cooperative Human Tissue Network and National Disease Research Interchange","award":["CA143748"],"award-info":[{"award-number":["CA143748"]}]},{"name":"Cooperative Human Tissue Network and National Disease Research Interchange","award":["AI066313"],"award-info":[{"award-number":["AI066313"]}]},{"name":"Cooperative Human Tissue Network and National Disease Research Interchange","award":["AI053481"],"award-info":[{"award-number":["AI053481"]}]},{"name":"BMS \u2018Freedom to Discover\u2019 Award"},{"name":"VA Merit Award","award":["U19 AI 1066328"],"award-info":[{"award-number":["U19 AI 1066328"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2013,8]]},"abstract":"Summary<\/jats:title>Hepatic CD<\/jats:styled-content>1d\u2010restricted and natural killer T<\/jats:styled-content>\u2010cell populations are heterogeneous. Classical \u2018type 1\u2032 \u03b1\u2010galactosylceramide\u2010reactive CD<\/jats:styled-content>1d\u2010restricted T<\/jats:styled-content> cells express \u2018invariant\u2019 TCR<\/jats:styled-content>\u03b1 (\u2018iNKT<\/jats:styled-content>\u2019). iNKT<\/jats:styled-content> dominating rodent liver are implicated in inflammation, including in hepatitis models. Low levels of iNKT<\/jats:styled-content> are detected in human liver, decreased in subjects with chronic hepatitis C (CHC<\/jats:styled-content>). However, high levels of human hepatic CD<\/jats:styled-content>161\u00b1<\/jats:sup>CD<\/jats:styled-content>56\u00b1<\/jats:sup> noninvariant pro\u2010inflammatory CD<\/jats:styled-content>1d\u2010restricted \u2018type 2\u2032 T<\/jats:styled-content> cells have been identified in vitro. Unlike rodents, healthy human hepatocytes only express trace and intracellular CD<\/jats:styled-content>1d. Total hepatic CD<\/jats:styled-content>1d appears to be increased in CHC<\/jats:styled-content> and primary biliary cirrhosis. Direct ex vivo analysis of human intrahepatic lymphocytes (IHL<\/jats:styled-content>), including matched ex vivo versus in vitro expanded IHL<\/jats:styled-content>, demonstrated detectable noninvariant CD<\/jats:styled-content>1d reactivity in substantial proportions of HCV<\/jats:styled-content>\u2010positive livers and significant fractions of HCV<\/jats:styled-content>\u2010negative livers. However, \u03b1\u2010galactosylceramide\u2010reactive iNKT<\/jats:styled-content> were detected only relatively rarely. Liver CD<\/jats:styled-content>1d\u2010restricted IHL<\/jats:styled-content> produced IFN<\/jats:styled-content>\u03b3, variable levels of IL<\/jats:styled-content>\u201010 and modest levels of Th2 cytokines IL<\/jats:styled-content>\u20104 and IL<\/jats:styled-content>\u201013 ex vivo. In a novel FACS<\/jats:styled-content> assay, a major fraction (10\u201320%) of hepatic T<\/jats:styled-content> cells rapidly produced IFN<\/jats:styled-content>\u03b3 and up\u2010regulated activation marker CD<\/jats:styled-content>69 in response to CD<\/jats:styled-content>1d. As previously only shown with murine iNKT<\/jats:styled-content>, noninvariant human CD<\/jats:styled-content>1d\u2010specific responses were also augmented by IL<\/jats:styled-content>\u201012. Interestingly, CD<\/jats:styled-content>1d was found selectively expressed on the surface of hepatocytes in CHC<\/jats:styled-content>, but not those CHC<\/jats:styled-content> subjects with history of alcohol usage or resolved CHC. In contrast to hepatic iNKT<\/jats:styled-content>, noninvariant IFN<\/jats:styled-content>\u03b3\u2010producing type 2 CD<\/jats:styled-content>1d\u2010reactive NKT<\/jats:styled-content> cells are commonly detected in CHC<\/jats:styled-content>, together with cognate ligand CD<\/jats:styled-content>1d, implicating them in CHC<\/jats:styled-content> liver damage.<\/jats:p>","DOI":"10.1111\/jvh.12081","type":"journal-article","created":{"date-parts":[[2013,3,13]],"date-time":"2013-03-13T01:10:37Z","timestamp":1363137037000},"page":"556-565","source":"Crossref","is-referenced-by-count":22,"title":["Ex vivo<\/i> analysis of resident hepatic pro\u2010inflammatory CD<\/scp>1d\u2010reactive T cells and hepatocyte surface CD<\/scp>1d expression in hepatitis C"],"prefix":"10.1111","volume":"20","author":[{"given":"K.","family":"Yanagisawa","sequence":"first","affiliation":[{"name":"Department of Medicine Beth Israel Deaconess Medical Centre Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Medicine Beth Israel Deaconess Medical Centre Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. J.","family":"van der Vliet","sequence":"additional","affiliation":[{"name":"Department of Medicine Beth Israel Deaconess Medical Centre Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine Beth Israel Deaconess Medical Centre Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Alatrakchi","sequence":"additional","affiliation":[{"name":"Department of Medicine Beth Israel Deaconess Medical Centre Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Golden\u2010Mason","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology\/Hepatology University of Colorado Denver Health Sciences Center Denver CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Schuppan","sequence":"additional","affiliation":[{"name":"Department of Medicine Beth Israel Deaconess Medical Centre Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. J.","family":"Koziel","sequence":"additional","affiliation":[{"name":"Department of Medicine Beth Israel Deaconess Medical Centre Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. R.","family":"Rosen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology\/Hepatology University of Colorado Denver Health Sciences Center Denver CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. A.","family":"Exley","sequence":"additional","affiliation":[{"name":"Department of Medicine Beth Israel Deaconess Medical Centre Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,3,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathol.1.110304.100230"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpgasthep0961"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.25.022106.141602"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2006.00838.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39133"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2009.01081.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-009-8152-3"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2011-300620"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20433"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2008.03.003"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199811)28:11<3448::AID-IMMU3448>3.0.CO;2-5"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(98)80206-7"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199908)29:08<2406::AID-IMMU2406>3.0.CO;2-F"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2000.19362"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(02)00072-7"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.4.1775"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132629"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.051604498"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.4.1519"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.2.1417"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.3.2159"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-006-0215-x"},{"key":"e_1_2_7_24_1","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.4049\/jimmunol.159.3.1216","article-title":"Mouse CD1 is mainly expressed on hemopoietic\u2010derived cells","volume":"159","author":"Brossay L","year":"1997","journal-title":"J Immunol"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-5890(98)00055-8"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2000.00001.x"},{"key":"e_1_2_7_27_1","first-page":"561","article-title":"Tissue distribution of the non\u2010polymorphic major histocompatibility complex class I\u2010like molecule, CD1d","volume":"80","author":"Canchis PW","year":"1993","journal-title":"Immunology"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510280303"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.3.1413"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2009.07.002"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200939800"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(09)01201-2"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2904"},{"key":"e_1_2_7_34_1","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1084\/jem.186.1.109","article-title":"Requirements for CD1d recognition by human invariant Va24+CD4\u2010CD8\u2010 T cells","volume":"186","author":"Exley M","year":"1997","journal-title":"J Exp Med"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.36020"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2008.03.009"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.5.867"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.6.3114"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1086\/378503"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.7.4046"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.21.10785-10790.2002"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.6.3147"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510290605"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.040566697"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200007)30:7<1919::AID-IMMU1919>3.0.CO;2-3"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22401"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.7.921"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00305-9"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.10.5531"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.im1411s90"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1002"},{"key":"e_1_2_7_52_1","first-page":"3226","article-title":"Adoptive immunotherapy with liver allograft\u2010derived lymphocytes induces anti\u2010HCV activity after liver transplantation in humans and humanized mice","volume":"119","author":"Ohira M","year":"2009","journal-title":"J Clin Invest"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2010.11.010"}],"container-title":["Journal of Viral Hepatitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvh.12081","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvh.12081","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.12081","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T09:00:51Z","timestamp":1696237251000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvh.12081"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3,11]]},"references-count":52,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2013,8]]}},"alternative-id":["10.1111\/jvh.12081"],"URL":"https:\/\/doi.org\/10.1111\/jvh.12081","archive":["Portico"],"relation":{},"ISSN":["1352-0504","1365-2893"],"issn-type":[{"value":"1352-0504","type":"print"},{"value":"1365-2893","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,3,11]]}}}