{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:41:31Z","timestamp":1789656091228,"version":"4.0.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,6,6]],"date-time":"2019-06-06T00:00:00Z","timestamp":1559779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2019.01319","type":"journal-article","created":{"date-parts":[[2019,6,6]],"date-time":"2019-06-06T14:19:30Z","timestamp":1559830770000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Ex vivo Detection and Characterization of Hepatitis B Virus-Specific CD8+ T Cells in Patients Considered Immune Tolerant"],"prefix":"10.3389","volume":"10","author":[{"given":"Pil Soo","family":"Sung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Jun","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Hee","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Won","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Byul","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gil Won","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Chul","family":"Nam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Won","family":"Jang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si Hyun","family":"Bae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Young","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eui-Cheol","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Hyung","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Kew","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2019,6,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"108","DOI":"10.3350\/cmh.2017.0068","article-title":"Management of chronic hepatitis B patients in immunetolerant phase: what latest guidelines recommend","volume":"24","author":"Wong","year":"2018","journal-title":"Clin Mol Hepatol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1038\/nri.2016.69","article-title":"Immune responses and immunopathology in acute and chronic viral hepatitis","volume":"16","author":"Shin","year":"2016","journal-title":"Nat Rev Immunol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2053","DOI":"10.1016\/S0140-6736(14)60220-8","article-title":"Hepatitis B virus infection","volume":"384","author":"Trepo","year":"2014","journal-title":"Lancet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1002\/hep.28156","article-title":"American Association for the Study of liver D. AASLD guidelines for treatment of chronic hepatitis B","volume":"63","author":"Terrault","year":"2016","journal-title":"Hepatology"},{"key":"B5","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.jhep.2017.03.021","article-title":"Electronic address: easloffice@easloffice","volume":"67","year":"2017","journal-title":"J Hepatol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1038\/nri3277","article-title":"The impact of differential antiviral immunity in children and adults","volume":"12","author":"Prendergast","year":"2012","journal-title":"Nat Rev Immunol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1111\/liv.12530","article-title":"Safety and immunogenicity of therapeutic DNA vaccine with antiviral drug in chronic HBV patients and its immunogenicity in mice","volume":"35","author":"Yoon","year":"2015","journal-title":"Liver Int."},{"key":"B8","doi-asserted-by":"publisher","first-page":"9369","DOI":"10.1128\/JVI.79.15.9369-9380.2005","article-title":"Stealth and cunning: hepatitis B and hepatitis C viruses","volume":"79","author":"Wieland","year":"2005","journal-title":"J Virol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1791","DOI":"10.1053\/j.gastro.2018.01.044","article-title":"HBV Bypasses the innate immune response and does not protect HCV from antiviral activity of interferon","volume":"154","author":"Mutz","year":"2018","journal-title":"Gastroenterology"},{"key":"B10","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1053\/j.gastro.2018.10.032","article-title":"Targeting innate and adaptive immune responses to cure chronic HBV infection","volume":"156","author":"Gehring","year":"2019","journal-title":"Gastroenterology"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1053\/j.gastro.2009.06.054","article-title":"Temporal analysis of early immune responses in patients with acute hepatitis B virus infection","volume":"137","author":"Dunn","year":"2009","journal-title":"Gastroenterology"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1172\/JCI44198","article-title":"IL-21 is pivotal in determining age-dependent effectiveness of immune responses in a mouse model of human hepatitis B","volume":"121","author":"Publicover","year":"2011","journal-title":"J Clin Invest."},{"key":"B13","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1053\/j.gastro.2012.06.009","article-title":"Preserved T-cell function in children and young adults with immune-tolerant chronic hepatitis B","volume":"143","author":"Kennedy","year":"2012","journal-title":"Gastroenterology."},{"key":"B14","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1053\/j.gastro.2016.07.012","article-title":"HBV DNA integration and clonal hepatocyte expansion in chronic hepatitis B patients considered immune tolerant","volume":"151","author":"Mason","year":"2016","journal-title":"Gastroenterology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1007\/s00281-017-0641-1","article-title":"Tolerance and immunity to pathogens in early life: insights from HBV infection","volume":"39","author":"Hong","year":"2017","journal-title":"Semin Immunopathol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1093\/infdis\/jix506","article-title":"Nucleos(t)ide analogue treatment for patients with Hepatitis B Virus (HBV) e antigen-positive chronic HBV genotype C infection: a nationwide, multicenter, retrospective study","volume":"216","author":"Chang","year":"2017","journal-title":"J Infect Dis"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032622","article-title":"A large population histology study showing the lack of association between ALT elevation and significant fibrosis in chronic hepatitis B","author":"Seto","year":"2012","journal-title":"PLoS ONE."},{"key":"B18","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1111\/j.1365-2893.2008.00989.x","article-title":"High prevalence of significant histology in asymptomatic chronic hepatitis B patients with genotype C and high serum HBV DNA levels","volume":"15","author":"Park","year":"2008","journal-title":"J Viral Hepat."},{"key":"B19","doi-asserted-by":"publisher","first-page":"13293","DOI":"10.3748\/wjg.v20.i37.13293","article-title":"Update on hepatitis B virus infection","volume":"20","author":"You","year":"2014"},{"key":"B20","doi-asserted-by":"publisher","first-page":"5427","DOI":"10.3748\/wjg.v20.i18.5427","article-title":"Hepatitis B virus genotypes: global distribution and clinical importance","volume":"20","author":"Sunbul","year":"2014","journal-title":"World J Gastroenterol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1136\/gut.2003.033324","article-title":"Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma","volume":"53","author":"Chan","year":"2004","journal-title":"Gut"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1002\/hep.29800","article-title":"Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance","volume":"67","author":"Terrault","year":"2018","journal-title":"Hepatology"},{"key":"B23","doi-asserted-by":"publisher","first-page":"9782","DOI":"10.1128\/JVI.00475-08","article-title":"The kinetics of hepatitis C virus-specific CD8 T-cell responses in the blood mirror those in the liver in acute hepatitis C virus infection","volume":"82","author":"Shin","year":"2008","journal-title":"J Virol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"4215","DOI":"10.1128\/JVI.02844-06","article-title":"Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection","volume":"81","author":"Boni","year":"2007","journal-title":"J Virol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1002\/hep.27805","article-title":"Re-evaluation of hepatitis B virus clinical phases by systems biology identifies unappreciated roles for the innate immune response and B cells","volume":"62","author":"Vanwolleghem","year":"2015","journal-title":"Hepatology."},{"key":"B26","doi-asserted-by":"publisher","first-page":"413","DOI":"10.3904\/kjim.2013.28.4.413","article-title":"Recent trends in hepatitis B virus infection in the general Korean population","volume":"28","author":"Kim","year":"2013","journal-title":"Korean J Intern Med"},{"key":"B27","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1002\/hep.27771","article-title":"Adaptation of the hepatitis B virus core protein to CD8(+) T-cell selection pressure","volume":"62","author":"Kefalakes","year":"2015","journal-title":"Hepatology"},{"key":"B28","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1084\/jem.20121172","article-title":"Up-regulation of a death receptor renders antiviral T cells susceptible to NK cell-mediated deletion","volume":"210","author":"Peppa","year":"2013","journal-title":"J Exp Med"},{"key":"B29","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1586\/erv.10.66","article-title":"MHC-peptide tetramers for the analysis of antigen-specific T cells","volume":"9","author":"Sims","year":"2010","journal-title":"Expert Rev Vaccines"},{"key":"B30","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.clim.2007.06.010","article-title":"The high prevalence of the I27 mutant HBcAg18-27 epitope in Chinese HBV-infected patients and its cross-reactivity with the V27 prototype epitope","volume":"125","author":"Liu","year":"2007","journal-title":"Clin Immunol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/369407a0","article-title":"Natural variants of cytotoxic epitopes are T-cell receptor antagonists for antiviral cytotoxic T cells","volume":"369","author":"Bertoletti","year":"1994","journal-title":"Nature."},{"key":"B32","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1136\/gutjnl-2018-316644","article-title":"Phenotype and function of HBV-specific T cells is determined by the targeted epitope in addition to the stage of infection","volume":"68","author":"Hoogeveen","year":"2018","journal-title":"Gut."},{"key":"B33","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1172\/JCI92812","article-title":"Hepatitis B virus-specific T cells associate with viral control upon nucleos(t)ide-analogue therapy discontinuation","volume":"128","author":"Rivino","year":"2018","journal-title":"J Clin Invest."},{"key":"B34","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1136\/gutjnl-2018-316641","article-title":"Phenotypic and functional differences of HBV core-specific versus HBV polymerase-specific CD8+ T cells in chronically HBV-infected patients with low viral load","volume":"68","author":"Schuch","year":"2019","journal-title":"Gut."},{"key":"B35","doi-asserted-by":"publisher","first-page":"3532","DOI":"10.1128\/JVI.80.7.3532-3540.2006","article-title":"Expression of the interleukin-7 receptor alpha chain (CD127) on virus-specific CD8+ T cells identifies functionally and phenotypically defined memory T cells during acute resolving hepatitis B virus infection","volume":"80","author":"Boettler","year":"","journal-title":"J Virol. ("},{"key":"B36","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1136\/gutjnl-2018-317959","article-title":"HBV antiviral immunity: not all CD8 T cells are born equal","volume":"68","author":"Bertoletti","year":"2019","journal-title":"Gut."},{"key":"B37","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1053\/j.gastro.2016.09.038","article-title":"\u201cTo be or not to be\u201d: immune tolerance in chronic hepatitis B","volume":"151","author":"Protzer","year":"2016","journal-title":"Gastroenterology"},{"key":"B38","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1136\/gut.2008.163600","article-title":"Early kinetics of innate and adaptive immune responses during hepatitis B virus infection","volume":"58","author":"Fisicaro","year":"2009","journal-title":"Gut"},{"key":"B39","doi-asserted-by":"publisher","first-page":"10986","DOI":"10.1128\/JVI.01124-08","article-title":"Host ethnicity and virus genotype shape the hepatitis B virus-specific T-cell repertoire","volume":"82","author":"Tan","year":"2008","journal-title":"J Virol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1186\/1743-422X-8-199","article-title":"Dynamic changes of cytotoxic T lymphocytes (CTLs), natural killer (NK) cells, and natural killer T (NKT) cells in patients with acute hepatitis B infection","volume":"8","author":"Li","year":"2011","journal-title":"Virol J"},{"key":"B41","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1016\/j.molimm.2007.07.038","article-title":"PD-1 upregulation is associated with HBV-specific T cell dysfunction in chronic hepatitis B patients","volume":"45","author":"Peng","year":"2008","journal-title":"Mol Immunol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"4551","DOI":"10.3748\/wjg.14.4551","article-title":"Programmed death-1 expression is associated with the disease status in hepatitis B virus infection","volume":"14","author":"Ye","year":"2008","journal-title":"World J Gastroenterol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.1084\/jem.20162115","article-title":"IL-2(high) tissue-resident T cells in the human liver: sentinels for hepatotropic infection","volume":"214","author":"Pallett","year":"2017","journal-title":"J Exp Med"},{"key":"B44","doi-asserted-by":"publisher","first-page":"3512","DOI":"10.1016\/j.celrep.2018.05.057","article-title":"Age-related decline in primary CD8(+) T cell responses is associated with the development of senescence in virtual memory CD8(+) T cells","volume":"23","author":"Quinn","year":"2018","journal-title":"Cell Rep"},{"key":"B45","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/s41467-018-08096-8","article-title":"Breakdown of adaptive immunotolerance induces hepatocellular carcinoma in HBsAg-tg mice","volume":"10","author":"Zong","year":"2019","journal-title":"Nat Commun."}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2019.01319\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,6,6]],"date-time":"2019-06-06T14:19:35Z","timestamp":1559830775000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2019.01319\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,6]]},"references-count":45,"alternative-id":["10.3389\/fimmu.2019.01319"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2019.01319","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,6]]},"article-number":"1319"}}