{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T04:53:37Z","timestamp":1764996817883},"reference-count":42,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2007,2,8]],"date-time":"2007-02-08T00:00:00Z","timestamp":1170892800000},"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":[[2007,7]]},"abstract":"<jats:p><jats:bold>Summary.\u2002<\/jats:bold> CD4<jats:sup>+<\/jats:sup> T\u2010cell responses are important for the outcome of hepatitis C virus (HCV) infection. However, the functional status of HCV\u2010specific CD4<jats:sup>+<\/jats:sup> T cells in persistent infection is poorly understood. It is generally recognized that proliferative capacity of HCV\u2010specific CD4<jats:sup>+<\/jats:sup> T cells is weak or absent in persistent infection, but whether this results from deletion of antigen\u2010specific cells or represents maintenance of antigen\u2010specific but poorly proliferative populations is not defined. We used a set of <jats:italic>ex vivo<\/jats:italic> assays to evaluate the functionality of HCV specific CD4<jats:sup>+<\/jats:sup> T cells in persistent and resolved infection. Peripheral blood mononuclear cells (PBMC) from 24 prospectively recruited HCV polymerase chain reaction (PCR) positive individuals, 12 spontaneously resolved individuals (i.e. anti\u2010HCV+, PCR\u2212) and 11 healthy controls were analysed for interferon\u2010<jats:italic>\u03b3<\/jats:italic> (IFN\u2010<jats:italic>\u03b3<\/jats:italic>) and interleukin 2 (IL\u20102) secretion by enzyme linked immunospot assays (ELISpot). HCV\u2010specific CD4<jats:sup>+<\/jats:sup> proliferative responses of carboxy fluorescein succinimidyl ester\u2010labelled PBMC were assessed using a sensitive single cell flow cytometric assay. Sustained IFN\u2010<jats:italic>\u03b3<\/jats:italic> ELISpot responses were observed in the PCR+ group. However, proliferation of HCV\u2010specific CD4<jats:sup>+<\/jats:sup> T cells in the PCR+ group was substantially reduced on a per cell basis, in parallel to IL\u20102 secretion, compared with responses in the PCR\u2212 group. In PCR\u2212 individuals, a strong relationship between cytokine secretion and proliferative capacity was seen. However, in PCR+ individuals, IFN\u2010<jats:italic>\u03b3<\/jats:italic> secretion far exceeded proliferative capacity. During persistent HCV infection, some CD4<jats:sup>+<\/jats:sup> T\u2010cell specificities appear to be lost, as measured using a range of techniques, but others, potentially important, are maintained as IFN\u2010<jats:italic>\u03b3<\/jats:italic> secretors but with low proliferative capacity even using a highly sensitive assay. Such subsets may yet play a significant role <jats:italic>in vivo<\/jats:italic> and also provide a template for modulation in immunotherapeutic interventions.<\/jats:p>","DOI":"10.1111\/j.1365-2893.2007.00842.x","type":"journal-article","created":{"date-parts":[[2007,2,8]],"date-time":"2007-02-08T09:32:17Z","timestamp":1170927137000},"page":"492-502","source":"Crossref","is-referenced-by-count":25,"title":["Analysis of the relationship between cytokine secretion and proliferative capacity in hepatitis C virus 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