{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:33:41Z","timestamp":1791293621316,"version":"4.1.0"},"reference-count":66,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,1,16]]},"abstract":"<jats:p>Vigorous proliferative CD4+ T cell responses are the hallmark of spontaneous clearance of acute hepatitis C virus (HCV) infection, whereas comparable responses are absent in chronically evolving infection. Here, we comprehensively characterized the breadth, specificity, and quality of the HCV-specific CD4+ T cell response in 31 patients with acute HCV infection and varying clinical outcomes. We analyzed in vitro T cell expansion in the presence of interleukin-2, and ex vivo staining with HCV peptide-loaded MHC class II tetramers. Surprisingly, broadly directed HCV-specific CD4+ T cell responses were universally detectable at early stages of infection, regardless of the clinical outcome. However, persistent viremia was associated with early proliferative defects of the HCV-specific CD4+ T cells, followed by rapid deletion of the HCV-specific response. Only early initiation of antiviral therapy was able to preserve CD4+ T cell responses in acute, chronically evolving infection. Our results challenge the paradigm that HCV persistence is the result of a failure to prime HCV-specific CD4+ T cells. Instead, broadly directed HCV-specific CD4+ T cell responses are usually generated, but rapid exhaustion and deletion of these cells occurs in the majority of patients. The data further suggest a short window of opportunity to prevent the loss of CD4+ T cell responses through antiviral therapy.<\/jats:p>","DOI":"10.1084\/jem.20100388","type":"journal-article","created":{"date-parts":[[2012,1,2]],"date-time":"2012-01-02T20:54:03Z","timestamp":1325537643000},"page":"61-75","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":213,"title":["Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence"],"prefix":"10.1084","volume":"209","author":[{"given":"Julian","family":"Schulze zur Wiesch","sequence":"first","affiliation":[{"name":"Gastrointestinal Unit 1 , 2 , and 3"},{"name":"Infectious Disease Division 1 , 2 , and 3"},{"name":"Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 1 , 2 , and 3"},{"name":"1. Medizinische Klinik, Universit\u00e4tsklinikum Hamburg Eppendorf, D-20246 Hamburg, Germany 4"},{"name":"Heinrich Pette Institut-Leibniz Institute for Experimental Virology, D-20251 Hamburg, Germany 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Ciuffreda","sequence":"additional","affiliation":[{"name":"Gastrointestinal Unit 1 , 2 , and 3"},{"name":"Infectious Disease Division 1 , 2 , and 3"},{"name":"Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 1 , 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lia","family":"Lewis-Ximenez","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Hepatites Virais, Instituto Oswaldo Cruz, Funda\u00e7\u00e3o Oswaldo Cruz, 21040 Rio de Janeiro, RJ, Brazil 8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Kasprowicz","sequence":"additional","affiliation":[{"name":"Gastrointestinal Unit 1 , 2 , and 3"},{"name":"Infectious Disease Division 1 , 2 , and 3"},{"name":"Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 1 , 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian E.","family":"Nolan","sequence":"additional","affiliation":[{"name":"Gastrointestinal Unit 1 , 2 , and 3"},{"name":"Infectious Disease Division 1 , 2 , and 3"},{"name":"Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 1 , 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Streeck","sequence":"additional","affiliation":[{"name":"Gastrointestinal Unit 1 , 2 , and 3"},{"name":"Infectious Disease Division 1 , 2 , and 3"},{"name":"Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 1 , 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasneet","family":"Aneja","sequence":"additional","affiliation":[{"name":"Gastrointestinal Unit 1 , 2 , and 3"},{"name":"Infectious Disease Division 1 , 2 , and 3"},{"name":"Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 1 , 2 , and 3"},{"name":"Gastrointestinal Unit 1 , 2 , and 3"},{"name":"Infectious Disease Division 1 , 2 , and 3"},{"name":"Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 1 , 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura L.","family":"Reyor","sequence":"additional","affiliation":[{"name":"Gastrointestinal Unit 1 , 2 , and 3"},{"name":"Infectious Disease Division 1 , 2 , and 3"},{"name":"Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 1 , 2 , and 3"},{"name":"Gastrointestinal Unit 1 , 2 , and 3"},{"name":"Infectious Disease Division 1 , 2 , and 3"},{"name":"Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 1 , 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd M.","family":"Allen","sequence":"additional","affiliation":[{"name":"Gastrointestinal Unit 1 , 2 , and 3"},{"name":"Infectious Disease Division 1 , 2 , and 3"},{"name":"Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 1 , 2 , and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ansgar W.","family":"Lohse","sequence":"additional","affiliation":[{"name":"1. 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