{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:55:58Z","timestamp":1791176158969,"version":"4.1.0"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":4353,"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":[[2003,10]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>The pathogenesis of liver cell injury during chronic hepatitis C (CHC) is poorly understood. The cellular immune response is thought to play a key role in both inhibition of viral replication and liver pathology. However, little is currently known about which lymphocyte populations and which immune effectors contribute to or control liver damage. We investigated a panel of 15 phenotypic and functional markers of intrahepatic T\u2013lymphocyte subsets irrespective of their antigen specificity in 48 hepatitis C virus (HCV)\u2013infected patients and 8 healthy control subjects. Lymphocyte characteristics were evaluated from liver biopsy specimens both at gene expression level by real\u2013time quantitative reverse\u2013transcription polymerase chain reaction (RT\u2013PCR) and by immunochemistry, in relation with the degree of liver injury and with intrahepatic HCV\u2013RNA levels. As compared with controls, we found major changes in T\u2013lymphocyte subsets in HCV\u2013infected patients, with a significant decrease of T\u2013cell antigen receptor (TCR) \u03b4 and CD56 gene expression, associated with a concomitant increase of TCR\u03b1 and CD8\u03b2 that were correlated with cytotoxic factors, proinflammatory chemokines, and chemokine receptors including peforin, interferon gamma (IFN\u2013\u03b3), tumor necrosis factor \u03b1 (TNF\u2013\u03b1), RANTES, and CXCR3. The gene expression of CD8\u03b2, a specific marker for conventional TCR\u03b1<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup> lymphocytes, was correlated by multivariate analysis with both alanine aminotransferase (ALT) serum levels and histologic activity index. Furthermore, CD8 staining was observed by immunochemistry in the areas of lobular and piecemeal necrosis. In contrast, no lymphocyte marker was correlated with viral load, measured both in serum and in liver. In conclusion, these results strongly suggest key roles for CD8<jats:sup>+<\/jats:sup> T cells as effectors of liver damage during chronic HCV infection and for their inability to control viral replication. (Hepatology 2003;38:829-841).<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.1840380409","type":"journal-article","created":{"date-parts":[[2007,3,10]],"date-time":"2007-03-10T22:34:45Z","timestamp":1173566085000},"page":"829-841","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":72,"title":["Phenotypic and Functional Characterization of Intrahepatic T Lymphocytes During Chronic Hepatitis C"],"prefix":"10.1097","volume":"38","author":[{"given":"Vincent","family":"Leroy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Vigan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Francois","family":"Mosnier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Dufeu-Duchesne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Pernollet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Zarski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice N.","family":"Marche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyne","family":"Jouvin-Marche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"10.1002\/hep.1840380409-BIB1","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/S1074-7613(00)80044-8","volume":"10","author":"Cooper","year":"1999","journal-title":"Immunity"},{"key":"10.1002\/hep.1840380409-BIB2","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/S0016-5085(99)70353-7","volume":"117","author":"Gerlach","year":"1999","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.1840380409-BIB3","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1086\/315450","volume":"181","author":"Gruner","year":"2000","journal-title":"J Infect Dis"},{"key":"10.1002\/hep.1840380409-BIB4","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1084\/jem.191.9.1499","volume":"191","author":"Lechner","year":"2000","journal-title":"J Exp Med"},{"key":"10.1002\/hep.1840380409-BIB5","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1084\/jem.194.10.1395","volume":"194","author":"Thimme","year":"2001","journal-title":"J Exp Med"},{"key":"10.1002\/hep.1840380409-BIB6","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/S1074-7613(01)00245-X","volume":"15","author":"Erickson","year":"2001","journal-title":"Immunity"},{"key":"10.1002\/hep.1840380409-BIB7","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1053\/gast.2001.21212","volume":"120","author":"Bain","year":"2001","journal-title":"Gastroenterology"},{"key":"10.1002\/hep.1840380409-BIB8","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1084\/jem.20011124","volume":"195","author":"Crotta","year":"2002","journal-title":"J Exp Med"},{"key":"10.1002\/hep.1840380409-BIB9","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.4049\/jimmunol.160.3.1479","volume":"160","author":"Wong","year":"1998","journal-title":"J Immunol"},{"key":"10.1002\/hep.1840380409-BIB10","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1053\/jhep.2000.9635","volume":"32","author":"Schirren","year":"2000","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840380409-BIB11","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1053\/jhep.2001.21162","volume":"33","author":"Chang","year":"2001","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840380409-BIB12","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1053\/jhep.2002.30293","volume":"35","author":"Rosen","year":"2002","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840380409-BIB13","doi-asserted-by":"crossref","first-page":"3448","DOI":"10.1002\/(SICI)1521-4141(199811)28:11<3448::AID-IMMU3448>3.0.CO;2-5","volume":"28","author":"Nuti","year":"1998","journal-title":"Eur J Immunol"},{"key":"10.1002\/hep.1840380409-BIB14","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1002\/hep.1840010511","volume":"1","author":"Knodell","year":"1981","journal-title":"Hepatology"},{"key":"10.1002\/hep.1840380409-BIB15","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1177\/27.4.109496","volume":"27","author":"Mason","year":"1979","journal-title":"J Histochem Cytochem"},{"key":"10.1002\/hep.1840380409-BIB16","first-page":"263","volume-title":"Rapid Cycle Real-Time PCR: Methods and Applications","author":"Jouvin-Marche","year":"2000","unstructured":", , Quantitative RT-PCR for the detection of T cell receptor transcripts in T lymphocyte populations using the light cycler technology. 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