{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T06:40:01Z","timestamp":1738219201326,"version":"3.34.0"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2008,1,22]],"date-time":"2008-01-22T00:00:00Z","timestamp":1200960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:p><jats:bold>Summary.\u2002<\/jats:bold>In order to understand the parameters associated with resolved hepatitis C virus (HCV)\u2010infection, we analysed the HCV\u2010specific T\u2010cell responses longitudinally in 13 injecting drug\u2010users (IDUs) with a prospectively identified acute HCV infection. Seven IDUs cleared HCV and six IDUs remained chronically infected. T\u2010cell responses were followed in the period needed to resolve and a comparable time span in chronic carriers.<jats:italic>Ex vivo<\/jats:italic>T\u2010cell responses were measured using interferon\u2010\u03b3 Elispot assays after stimulation with overlapping peptide pools spanning the complete HCV genome. CD4+<jats:italic>memory\u2010<\/jats:italic>T\u2010cell responses were determined after 12\u2010day stimulation with HCV proteins. The maximum response was compared between individuals. The T\u2010cell responses measured directly<jats:italic>ex vivo<\/jats:italic>were weak but significantly higher in resolvers compared to chronic carriers, whereas the CD4+<jats:italic>memory<\/jats:italic>\u2010T\u2010cell response was not different between resolvers and chronic carriers. However, HCV Core protein was targeted more often in chronic carriers compared to individuals resolving HCV infection. CD4+ T\u2010cell responses predominantly targeting nonstructural proteins were associated with resolved HCV infection. Interestingly, observation of<jats:italic>memory\u2010T\u2010cell<\/jats:italic>responses present before the documented HCV\u2010seroconversion suggests that reinfections in IDUs occur often. The presence of these responses however, were not predictive for the outcome of infection. However, a transition of the HCV\u2010specific CD4+<jats:italic>memory<\/jats:italic>\u2010T\u2010cell response from targeting Core to targeting nonstructural proteins during onset of infection was associated with a favourable outcome. Therefore, the specificity of the CD4+<jats:italic>memory<\/jats:italic>\u2010T\u2010cell responses measured after 12\u2010day expansion seems most predictive of resolved infection.<\/jats:p>","DOI":"10.1111\/j.1365-2893.2007.00963.x","type":"journal-article","created":{"date-parts":[[2008,5,12]],"date-time":"2008-05-12T01:31:41Z","timestamp":1210555901000},"page":"409-420","source":"Crossref","is-referenced-by-count":13,"title":["HCV\u2010specific T\u2010cell responses in injecting drug users: evidence for previous exposure to HCV and a role for CD4+ T cells focussing on nonstructural proteins in viral clearance"],"prefix":"10.1111","volume":"15","author":[{"given":"T. A.","family":"Ruys","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. M.","family":"Nanlohy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. H. S. B.","family":"Van Den Berg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Hassink","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Beld","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Van De Laar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Bruisten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Wit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Krol","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Prins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Lange","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Van Baarle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,1,30]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200107053450107"},{"issue":"5","key":"e_1_2_7_3_2","doi-asserted-by":"crossref","first-page":"S21","DOI":"10.1002\/hep.1840360704","article-title":"Course and outcome of hepatitis C","volume":"36","author":"Hoofnagle JH","year":"2002","journal-title":"Hepatology"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.21162"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80044-8"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)91691-1"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70353-7"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.9.1499"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030239"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.10.1395"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.24.12584-12595.2002"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20749"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.27024"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.202608299"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.12.5550-5558.2001"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/75063"},{"issue":"3","key":"e_1_2_7_17_2","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.4049\/jimmunol.160.3.1479","article-title":"Liver\u2010derived CTL in hepatitis C virus infection: breadth and specificity of responses in a cohort of persons with chronic infection","volume":"160","author":"Wong DK","year":"1998","journal-title":"J Immunol"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200425792"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-198802000-00010"},{"issue":"4","key":"e_1_2_7_20_2","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1128\/JCM.36.4.872-877.1998","article-title":"Different hepatitis C virus (HCV) RNA load profiles following seroconversion among injecting drug users without correlation with HCV genotype and serum alanine aminotransferase levels","volume":"36","author":"Beld M","year":"1998","journal-title":"J Clin Microbiol"},{"issue":"4","key":"e_1_2_7_21_2","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1182\/blood.V94.4.1183.416k15_1183_1191","article-title":"Low levels of hepatitis C virus RNA in serum, plasma, and peripheral blood mononuclear cells of injecting drug users during long antibody\u2010undetectable periods before seroconversion","volume":"94","author":"Beld M","year":"1999","journal-title":"Blood"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2005-864778"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.35.1.201-207.1997"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200411190-00013"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.11.6931"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-01-0432"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.3.1207"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200103)31:3<677::AID-IMMU677>3.0.CO;2-M"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.4.2210"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.06.015"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2006.05.013"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1009"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1088774"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.2.862-870.2003"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)70197-5"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.6.3603"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2003.12.003"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2005-864785"},{"issue":"2","key":"e_1_2_7_39_2","first-page":"71","article-title":"Detection of hepatitis C virus core protein in the glomeruli of patients with membranous glomerulonephritis","volume":"45","author":"Okada K","year":"1996","journal-title":"Clin Nephrol"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M407640200"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.12.6409-6419.2004"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118931"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(03)00668-1"},{"key":"e_1_2_7_44_2","doi-asserted-by":"publisher","DOI":"10.1086\/424491"},{"volume-title":"Frequent HCV Reinfection and Superinfection among Active Injecting Drug Users in Amsterdam","year":"2006","author":"Van De Laar TJW","key":"e_1_2_7_45_2"},{"key":"e_1_2_7_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2006.00812.x"},{"key":"e_1_2_7_47_2","doi-asserted-by":"publisher","DOI":"10.1086\/422605"},{"key":"e_1_2_7_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08435-0"},{"key":"e_1_2_7_49_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200405210-00005"}],"container-title":["Journal of Viral Hepatitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2893.2007.00963.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2893.2007.00963.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T06:13:23Z","timestamp":1738217603000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2893.2007.00963.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,1,30]]},"references-count":48,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2008,6]]}},"alternative-id":["10.1111\/j.1365-2893.2007.00963.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2893.2007.00963.x","archive":["Portico"],"relation":{},"ISSN":["1352-0504","1365-2893"],"issn-type":[{"type":"print","value":"1352-0504"},{"type":"electronic","value":"1365-2893"}],"subject":[],"published":{"date-parts":[[2008,1,30]]}}}