{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T04:16:03Z","timestamp":1787631363276,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Natural clearance of hepatitis C virus (HCV) infection occurs in about 25% of primary infections, but offers only partial protective immunity against re\u2010infections. This study hypothesised that long\u2010lived polyfunctional HCV\u2010specific CD8+ memory stem T cells (T\n                    <jats:sub>SCM<\/jats:sub>\n                    ) contribute to protective immunity in rare super\u2010clearer subjects who repeatedly clear viraemia. Six super\u2010clearers and four clearer\u2010chronic subjects who resolved a primary infection but subsequently developed chronic infection were studied at multiple timepoints. The T\n                    <jats:sub>SCM<\/jats:sub>\n                    population (CCR7+CD45RA+CD95+) was bulk sorted, labelled with CellTrace Violet (CTV), and stimulated in vitro for five days with cognate HCV peptide, IL\u20102\/IL\u201015, and autologous PBMCs. Functionality of the expanded HCV\u2010specific T\n                    <jats:sub>SCM<\/jats:sub>\n                    was assessed via the proliferation, multi\u2010potency, and stemness indices.\n                    <jats:styled-content>Total<\/jats:styled-content>\n                    HCV\u2010specific CD8+ T cells from super\u2010clearers exhibited enhanced proliferative recall capability compared with clearer\u2010chronics. Furthermore, super\u2010clearers exhibited higher HCV\u2010T\n                    <jats:sub>SCM<\/jats:sub>\n                    frequencies post\u2010expansion (22.35\u00a0\u00b1\u00a034.35\u00a0vs. 2.41\u00a0\u00b1\u00a09.83;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.0066). Notably, HCV\u2010T\n                    <jats:sub>SCM<\/jats:sub>\n                    in clearer\u2010chronics had \u2018stemness\u2019 indices of zero in samples before the re\u2010infection (i.e., no ability to generate T\n                    <jats:sub>SCM<\/jats:sub>\n                    as progeny), whereas super\u2010clearers consistently retained this key functional property. These findings suggest that the maintenance of self\u2010renewing HCV\u2010specific T\n                    <jats:sub>SCM<\/jats:sub>\n                    may underpin long\u2010term protective immunity against re\u2010infection and could inform vaccine design strategies targeting durable cellular memory.\n                  <\/jats:p>","DOI":"10.1002\/eji.70098","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T11:03:47Z","timestamp":1766055827000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Functional Antigen\u2010Specific CD8 T\n                    <sub>SCM<\/sub>\n                    Responses Are Associated with Repeated Clearance of Hepatitis C Virus Infection"],"prefix":"10.1002","volume":"55","author":[{"given":"Yanran","family":"Zhao","sequence":"first","affiliation":[{"name":"Viral Immunology Systems Program (VISP) The Kirby Institute University of New South Wales  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Institute  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Boo","sequence":"additional","affiliation":[{"name":"Burnet Institute  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Dietze","sequence":"additional","affiliation":[{"name":"Burnet Institute  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Hellard","sequence":"additional","affiliation":[{"name":"Burnet Institute  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Drummer","sequence":"additional","affiliation":[{"name":"Burnet Institute  Melbourne VIC Australia"},{"name":"Department of Microbiology Monash University  Clayton VIC Australia"},{"name":"Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity University of Melbourne  Melbourne VIC 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