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Chronic hepatitis C virus (HCV) infection causes dysfunction of several subsets of UTCs. This altered phenotype and function of UTCs can persist over time even after direct\u2010acting antiviral (DAA)\u2010mediated clearance of chronic HCV. However, it is less clear if and how UTCs respond in acute, symptomatic HCV infection, a rare clinical condition, and if rapid DAA treatment of such patients reverses the caused perturbations within UTCs. Here, we comprehensively analyzed the phenotype and reinvigoration capacity of three major UTC populations, mucosal\u2010associated invariant T (MAIT) cells, \u03b3\u03b4 T cells, and CD4 and CD8 double\u2010negative \u03b1\u03b2 T cells (DNT cells) before, during, and after DAA\u2010mediated clearance of acute symptomatic HCV infection. Furthermore, MAIT cell functionality was systematically studied. We observed a reduced frequency of MAIT cells. However, remaining cells presented with a near\u2010to\u2010normal phenotype in acute infection, which contrasted with a significant dysfunction upon stimulation that was not restored after viral clearance. Notably, DNT and \u03b3\u03b4 T cells displayed a strong activation ex\u2010vivo in acute HCV infection, which subsequently normalized during the treatment. In addition, DNT cell activation was specifically associated with liver inflammation and inflammatory cytokines. Altogether, these data provide evidence that UTCs respond in a cell type\u2010specific manner during symptomatic HCV infection. However, even if early treatment is initiated, long\u2010lasting imprints within UTCs remain over time.<\/jats:p>","DOI":"10.1002\/eji.202149457","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T11:07:52Z","timestamp":1638184072000},"page":"472-483","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Imprint of unconventional T\u2010cell response in acute hepatitis C persists despite successful early antiviral treatment"],"prefix":"10.1002","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1775-5947","authenticated-orcid":false,"given":"Yanqin","family":"Du","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology University Hospital Essen University of Duisburg\u2010Essen  Essen 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