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Indeed, effector cells were unable to perform immediate functions, despite expressing the tissue\u2010homing phenotype of effector memory cells (CCR7<jats:sup>\u2013<\/jats:sup>; semi\u2010effectors). However, since they promptly differentiated into full\u2010effectors upon IL\u20102 contact, we suggested that the inhibitory effect by environmental (possibly viral) factors on IL\u20102 production may have a pivotal role in generating the large population of semi\u2010effector CCR7<jats:sup>\u2013<\/jats:sup>\/IFN\u2010\u03b3<jats:sup>\u2013<\/jats:sup> CTL. In accord with this view, we report here strong evidence in support of circulating HCVcore protein (HCVcore) playing a central role in inhibiting effector CTL differentiation, but not memory CTL expansion. The regulatory HCVcore effect is related to inhibition of the signal transduction pathway instrumental for IL\u20102 production, supporting the evidence that IL\u20102 was capable both of pushing semi\u2010effector CTL to complete their effector cell program and of restoring the HCVcore\u2010dependent inhibitory effect. Therefore, the strength of CTL activation is dependent on the balance between the threshold of stimulatory signals and the viral interference capacities provided during priming.<\/jats:p>","DOI":"10.1002\/eji.200324540","type":"journal-article","created":{"date-parts":[[2004,2,4]],"date-time":"2004-02-04T12:00:38Z","timestamp":1075896038000},"page":"438-446","source":"Crossref","is-referenced-by-count":44,"title":["Subversion of effector CD8<sup>+<\/sup> T\u2004cell differentiation in acute hepatitis\u2004C virus infection: the role of the virus"],"prefix":"10.1002","volume":"34","author":[{"given":"Daniele","family":"Accapezzato","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vittorio","family":"Francavilla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pisana","family":"Rawson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Cerino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agostino","family":"Cividini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario\u2004U.","family":"Mondelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Barnaba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,2,3]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.100101.151926"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri778"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/44385"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni804"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni889"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/35065111"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1058867"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5489.92"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.7.953"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/88678"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI13296"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1064571"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020033"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020066"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020067"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020369"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20011612"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni908"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni912"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.141110"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.861"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200107053450107"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80044-8"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200103)31:3<894::AID-IMMU894>3.0.CO;2-I"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.10.5692"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.9.1499"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.10.1395"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200009)30:9<2479::AID-IMMU2479>3.0.CO;2-B"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.12.5550-5558.2001"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.12.6104-6113.2002"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.24.12423-12434.2002"},{"key":"e_1_2_7_32_2","doi-asserted-by":"crossref","first-page":"6681","DOI":"10.4049\/jimmunol.162.11.6681","article-title":"Presence of effector CD8+ T\u2004cells in hepatitis\u2004C virus\u2010exposed healthy seronegative donors.","volume":"162","author":"Scognamiglio P.","year":"1999","journal-title":"J. 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