{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:31:00Z","timestamp":1791268260158,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2006,6,16]],"date-time":"2006-06-16T00:00:00Z","timestamp":1150416000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2006,8]]},"abstract":"<jats:p>\n                    <jats:bold>Summary.\u2002<\/jats:bold>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells are thought to contribute to antiviral immune responses by secretion of cytokines thereby providing help to CD8\n                    <jats:sup>+<\/jats:sup>\n                    T and B cells. However, perforin\u2010positive cytotoxic CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells have been described in human immunodeficiency virus\u2010positive patients suggesting a role not only of CD8\n                    <jats:sup>+<\/jats:sup>\n                    but also of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells for killing virus\u2010infected cells. We investigated 76 patients with viral hepatitis [15 hepatitis B virus (HBV), 22 HBV\/hepatitis D virus and 17 hepatitis C virus (HCV)] for cytotoxic CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. The frequency of perforin\u2010positive CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells in viral hepatitis was highly variable ranging from &lt;1% to more than 25%. Perforin\u2010positive CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells displayed the phenotype of terminally differentiated effector cells (CD28\n                    <jats:sup>\u2212<\/jats:sup>\n                    , CD27\n                    <jats:sup>\u2212<\/jats:sup>\n                    ). The highest frequencies of CD4\n                    <jats:sup>+<\/jats:sup>\n                    cytotoxic T lymphocytes (CTLs) were found in patients with delta hepatitis (\n                    <jats:italic>P<\/jats:italic>\n                    \u2003=\u20030.04\n                    <jats:italic>vs<\/jats:italic>\n                    HBV and HCV patients), and the presence of CD4\n                    <jats:sup>+<\/jats:sup>\n                    CTLs was associated with elevated aspartate aminotransferase levels (\n                    <jats:italic>P<\/jats:italic>\n                    \u2003=\u20030.01) and decreased platelet counts (\n                    <jats:italic>P<\/jats:italic>\n                    \u2003=\u20030.03). Perforin\u2010positive CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells decreased in two individuals during spontaneous clearance of acute hepatitis C. Significant associations were found between the frequency of perforin\u2010expressing CD4\n                    <jats:sup>+<\/jats:sup>\n                    cells and age (\n                    <jats:italic>P<\/jats:italic>\n                    \u2003=\u20030.04), perforin\u2010positive CD8\n                    <jats:sup>+<\/jats:sup>\n                    cells (\n                    <jats:italic>P<\/jats:italic>\n                    \u2003&lt;\u20030.001) and perforin\u2010positive CD4\n                    <jats:sup>\u2212<\/jats:sup>\n                    \/CD8\n                    <jats:sup>\u2212<\/jats:sup>\n                    lymphoid cells (\n                    <jats:italic>P<\/jats:italic>\n                    \u2003=\u20030.002). Differentiated CD27\n                    <jats:sup>\u2212<\/jats:sup>\n                    effector CD4\n                    <jats:sup>+<\/jats:sup>\n                    CTLs can be detected in patients with viral hepatitis. In particular in patients with more advanced liver disease, the accumulation of perforin\u2010positive T cells with age could be one correlate for the more severe course of viral hepatitis in elderly individuals.\n                  <\/jats:p>","DOI":"10.1111\/j.1365-2893.2006.00723.x","type":"journal-article","created":{"date-parts":[[2006,6,16]],"date-time":"2006-06-16T12:18:37Z","timestamp":1150460317000},"page":"505-514","source":"Crossref","is-referenced-by-count":152,"title":["Cytotoxic CD4\n                    <sup>+<\/sup>\n                    T cells in viral hepatitis"],"prefix":"10.1111","volume":"13","author":[{"given":"N.","family":"Aslan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Yurdaydin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Wiegand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Greten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Ciner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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