{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:57:49Z","timestamp":1791176269276,"version":"4.1.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":4506,"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":[[2003,5]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Chronic hepatitis C is characterized by a weak or absent hepatitis C virus (HCV)\u2013specific CD4<jats:sup>+<\/jats:sup> T\u2013cell response in terms of antigen\u2013specific proliferation or interferon gamma (IFN\u2013\u03b3) secretion. To clarify whether this is due to the absence or functional impairment of antigen\u2013specific CD4<jats:sup>+<\/jats:sup> T cells we developed an assay that relies on the induced expression of the T\u2013cell activation marker CD25 and is therefore independent from cytokine secretion or proliferation. In 10 of 20 patients with chronic hepatitis C, a significant number of antigen\u2013specific activated CD4<jats:sup>+<\/jats:sup> T cells (mean 1.06%\/patient; range, 0% to 5.2% of CD4<jats:sup>+<\/jats:sup> T cells) could be shown, whereas antigen\u2013specific proliferation was present in only 1 of 20 patients. IFN\u2013\u03b3 secretion was absent in all 13 patients tested. However, significant antigen\u2013specific interleukin 10 (IL\u201310) and transforming growth factor \u03b2 (TGF\u2013\u03b2) secretion was present in 6 of 10 and 3 of 10 patients, respectively. In 8 patients with acute hepatitis C, irrespective of disease outcome, HCV\u2013specific CD4<jats:sup>+<\/jats:sup> T cells were detected in all patients and at a significantly higher frequency (mean 3.7%\/patient; range, 1.16% to 7.17%) in the first weeks of disease. A chronic course of disease was associated either with a loss of both IFN\u2013\u03b3 secretion and proliferation, resembling an anergic state, or a loss of T\u2013cell proliferation followed by a rapid decline in IFN\u2013\u03b3\u2013producing cells, corresponding to exhaustion of the specific immune response. In conclusion, functional changes of HCV\u2013specific CD4<jats:sup>+<\/jats:sup> T cells or failure to develop a long\u2013lasting T\u2013helper response may contribute to chronic hepatitis C viral persistence.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1053\/jhep.2003.50194","type":"journal-article","created":{"date-parts":[[2003,5,13]],"date-time":"2003-05-13T05:21:15Z","timestamp":1052803275000},"page":"1189-1198","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":176,"title":["Detection of Functionally Altered Hepatitis C Virus\u2013Specific Cd4+ T Cells in Acute and Chronic Hepatitis C"],"prefix":"10.1097","volume":"37","author":[{"given":"Axel","family":"Ulsenheimer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilman J.","family":"Gerlach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert H.","family":"Gruener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Christina","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl-Albrecht","family":"Schirren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winfried","family":"Schraut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhart","family":"Zachoval","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd R.","family":"Pape","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut 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