{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:35:55Z","timestamp":1791192955194,"version":"4.1.0"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":3349,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,7]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>A timely, efficient, and coordinated activation of both CD4 and CD8 T cell subsets following HCV infection is believed to be essential for HCV control. However, to what extent a failure of the individual T cell subsets can contribute to the high propensity of HCV to persist is still largely undefined. To address this issue, we analyzed the breadth, vigor, and quality of CD4 and CD8 responses simultaneously with panels of peptides covering the entire HCV sequence or containing the HLA-A2\u2013binding motif, and with recombinant HCV proteins in 16 patients with acute HCV infection by tetramer staining, ELISPOT, and intracellular cytokine staining for interferon \u03b3, interleukin (IL)-2, IL-4, and IL-10. Our results indicate that at clinical onset, CD8 responses are similarly weak and narrowly focused in both self-limited and chronically evolving infections. At this stage, CD4 responses are deeply impaired in patients with a chronic outcome as they are weak and of narrow specificity, unlike the strong, broad and T helper 1\u2013oriented CD4 responses associated with resolving infections. Only patients able to finally control infection show maturation of CD8 memory sustained by progressive expansion of CD127+ CD8 cells. Thus, a poor CD8 response in the acute stage of infection may enhance the overall probability of chronic viral persistence.<\/jats:bold>\n                                 <jats:bold>\n                                    In conclusion\n                                 <\/jats:bold>\n                                 <jats:bold>, the presence of functional CD4 responses represents one of the factors dictating the fate of infection by directly contributing to control of the virus and by promoting maturation of protective memory CD8 responses.<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.21242","type":"journal-article","created":{"date-parts":[[2006,6,27]],"date-time":"2006-06-27T07:26:57Z","timestamp":1151393217000},"page":"126-139","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":166,"title":["Outcome of acute hepatitis C is related to virus-specific CD4 function and maturation of antiviral memory CD8 responses"],"prefix":"10.1097","volume":"44","author":[{"given":"Simona","family":"Urbani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Amadei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Fisicaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Tola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Orlandini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Sacchelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Missale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Ferrari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-19-20241201","doi-asserted-by":"crossref","first-page":"12423","DOI":"10.1128\/JVI.76.24.12423-12434.2002","article-title":"Virusspecific CD8 lymphocytes share the same effectormemory phenotype but exhibit functional differences in acute hepatitis B and C.","volume":"76","author":"Urbani","year":"2002","journal-title":"J Virol"},{"key":"R2-19-20241201","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1084\/jem.194.10.1395","article-title":"Determinants of viral clearance and persistence during acute hepatitis C virus infection.","volume":"194","author":"Thimme","year":"2001","journal-title":"J Exp Med"},{"key":"R3-19-20241201","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1084\/jem.191.9.1499","article-title":"Analysis of successful immune responses in persons infected with hepatitis C virus.","volume":"191","author":"Lechner","year":"2000","journal-title":"J Exp Med"},{"key":"R4-19-20241201","doi-asserted-by":"crossref","first-page":"5550","DOI":"10.1128\/JVI.75.12.5550-5558.2001","article-title":"Sustained dysfunction of antiviral CD8 T lymphocytes after infection with hepatitis C 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