{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T19:04:45Z","timestamp":1770059085057,"version":"3.49.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2003,6,16]],"date-time":"2003-06-16T00:00:00Z","timestamp":1055721600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The factors influencing lymphocyte trafficking to the liver lobule during chronic hepaititis C virus (HCV) infection are currently not well defined. Interferon-\u03b3-inducible protein 10 (IP-10), a chemokine that recruits activated T lymphocytes, has recently been shown by in situ hybridization to be expressed in the liver during chronic HCV infection. This study sought to define the cellular source of IP-10 in the liver by immunohistochemistry, to examine the expression of its receptor, CXCR3, on T lymphocytes isolated from blood and liver tissue, and to correlate IP-10 expression with the histological markers of inflammation and fibrosis. IP-10 was expressed by hepatocytes but not by other cell types within the liver, and the most intense immunoreactivity was evident in the areas of lobular inflammation. The IP-10 receptor was expressed on a significantly higher proportion of T lymphocytes in the liver compared with blood. CD8 T lymphocytes, which predominate in the liver lobule, were almost uniformly CXCR3-positive. The expression of IP-10 mRNA correlated with lobular necroinflammatory activity but not with inflammation or fibrosis in the portal tracts. These findings suggest that IP-10 may be induced by HCV within hepatocytes and may be important in the pathogenesis of chronic HCV infection, as recruitment of inflammatory cells into the lobule is an important predictor of disease progression.<\/jats:p>","DOI":"10.1189\/jlb.0303093","type":"journal-article","created":{"date-parts":[[2003,8,29]],"date-time":"2003-08-29T20:50:15Z","timestamp":1062190215000},"page":"360-369","source":"Crossref","is-referenced-by-count":195,"title":["Expression of the chemokine IP-10 (CXCL10) by hepatocytes in chronic hepatitis C virus infection correlates with histological severity and lobular inflammation"],"prefix":"10.1093","volume":"74","author":[{"given":"Charles E","family":"Harvey","sequence":"first","affiliation":[{"name":"Viral Hepatitis Research Unit, Department of Gastroenterology, Prince of Wales Hospital , Sydney , New South Wales , Australia"}]},{"given":"Jeffrey J","family":"Post","sequence":"additional","affiliation":[{"name":"Inflammation Research Unit, Department of Pathology, Sydney Children\u2019s Hospital, and the School of Women\u2019s and Children\u2019s Health, University of New South Wales , Sydney , Australia"}]},{"given":"Patricia","family":"Palladinetti","sequence":"additional","affiliation":[{"name":"Inflammation Research Unit, Department of Pathology, Sydney Children\u2019s Hospital, and the School of Women\u2019s and Children\u2019s Health, University of New South Wales , Sydney , Australia"}]},{"given":"Anthony J","family":"Freeman","sequence":"additional","affiliation":[{"name":"Viral Hepatitis Research Unit, Department of Gastroenterology, Prince of Wales Hospital , Sydney , New South Wales , Australia"}]},{"given":"Rosemary A","family":"Ffrench","sequence":"additional","affiliation":[{"name":"Department of Immunology nd Infectious Diseases, Sydney Children\u2019s Hospital, and the School of Women\u2019s and Children\u2019s Health, University of New South Wales , Sydney , Australia"}]},{"given":"Rakesh K","family":"Kumar","sequence":"additional","affiliation":[{"name":"Inflammation Research Unit, Department of Pathology, Sydney Children\u2019s Hospital, and the School of Women\u2019s and Children\u2019s Health, University of New South Wales , Sydney , Australia"}]},{"given":"George","family":"Marinos","sequence":"additional","affiliation":[{"name":"Viral Hepatitis Research Unit, Department of Gastroenterology, Prince of Wales Hospital , Sydney , New South Wales , Australia"}]},{"given":"Andrew R","family":"Lloyd","sequence":"additional","affiliation":[{"name":"Inflammation Research Unit, Department of Pathology, Sydney Children\u2019s Hospital, and the School of Women\u2019s and Children\u2019s Health, University of New South Wales , Sydney , Australia"}]}],"member":"286","published-online":{"date-parts":[[2003,6,16]]},"reference":[{"key":"2023033100471263200_jlb0360-cit-B1","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1056\/NEJM198911303212202","article-title":"Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis","volume":"321","author":"Alter","year":"1989","journal-title":"N. Engl. J. Med."},{"key":"2023033100471263200_jlb0360-cit-B2","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1002\/hep.1840150402","article-title":"The pathology of hepatitis C","volume":"15","author":"Scheuer","year":"1992","journal-title":"Hepatology"},{"key":"2023033100471263200_jlb0360-cit-B3","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/S0167-5699(99)01518-2","article-title":"Prometheus through the looking glass: reflections on the hepatic immune system","volume":"20","author":"O\u2019Farrelly","year":"1999","journal-title":"Immunol. Today"},{"key":"2023033100471263200_jlb0360-cit-B4","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/0016-5085(93)90432-C","article-title":"Pathological diagnosis of chronic hepatitis C: a multicenter comparative study with chronic hepatitis B. The Hepatitis Interventional Therapy Group","volume":"104","author":"Lefkowitch","year":"1993","journal-title":"Gastroenterology"},{"key":"2023033100471263200_jlb0360-cit-B5","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/j.1600-0676.1993.tb00609.x","article-title":"Liver biopsy features of acute hepatitis C compared with hepatitis A, B, and non-A, non-B, non-C","volume":"13","author":"Kobayashi","year":"1993","journal-title":"Liver"},{"key":"2023033100471263200_jlb0360-cit-B6","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1002\/hep.1840150403","article-title":"The histological features of chronic hepatitis C and autoimmune chronic hepatitis: a comparative analysis","volume":"15","author":"Bach","year":"1992","journal-title":"Hepatology"},{"key":"2023033100471263200_jlb0360-cit-B7","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1056\/NEJM199506013322202","article-title":"Clinical outcomes after transfusion-associated hepatitis C","volume":"332","author":"Tong","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"2023033100471263200_jlb0360-cit-B8","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1056\/NEJM199608293350904","article-title":"Hepatitis C virus-associated fulminant hepatic failure","volume":"335","author":"Farci","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"2023033100471263200_jlb0360-cit-B9","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/0140-6736(93)90210-8","article-title":"Persistent hepatitis C viraemia without liver disease","volume":"341","author":"Brillanti","year":"1993","journal-title":"Lancet"},{"key":"2023033100471263200_jlb0360-cit-B10","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/j.1365-2893.1997.tb00178.x","article-title":"The role of immune responses in the pathogenesis of hepatitis C virus infection","volume":"4","author":"Koziel","year":"1997","journal-title":"J. Viral Hepat."},{"key":"2023033100471263200_jlb0360-cit-B11","first-page":"1368","article-title":"T-cell-mediated autologous hepatocytotoxicity in patients with chronic hepatitis C virus infection","volume":"22","author":"Liaw","year":"1995","journal-title":"Hepatology"},{"key":"2023033100471263200_jlb0360-cit-B12","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/S0140-6736(96)07524-1","article-title":"Chemokines: leucocyte recruitment and activation cytokines","volume":"349","author":"Adams","year":"1997","journal-title":"Lancet"},{"key":"2023033100471263200_jlb0360-cit-B13","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/33340","article-title":"Chemokines and leukocyte traffic","volume":"392","author":"Baggiolini","year":"1998","journal-title":"Nature"},{"key":"2023033100471263200_jlb0360-cit-B14","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1146\/annurev.immunol.15.1.675","article-title":"Human chemokines: an update","volume":"15","author":"Baggiolini","year":"1997","journal-title":"Annu. Rev. Immunol."},{"key":"2023033100471263200_jlb0360-cit-B15","first-page":"339","article-title":"The role of chemokines in the immunopathology of pulmonary disease","volume":"9","author":"Kunkel","year":"1999","journal-title":"Forum (Genova)"},{"key":"2023033100471263200_jlb0360-cit-B16","doi-asserted-by":"crossref","first-page":"3583","DOI":"10.4049\/jimmunol.156.10.3583","article-title":"\u201cThe good, the bad, and the ugly.\u201d The role of chemokines in models of human disease","volume":"156","author":"Strieter","year":"1996","journal-title":"J. Immunol."},{"key":"2023033100471263200_jlb0360-cit-B17","doi-asserted-by":"crossref","first-page":"6236","DOI":"10.4049\/jimmunol.163.11.6236","article-title":"Chemokine and chemokine receptor interactions provide a mechanism for selective T cell recruitment to specific liver compartments within hepatitis C-infected liver","volume":"163","author":"Shields","year":"1999","journal-title":"J. Immunol."},{"key":"2023033100471263200_jlb0360-cit-B18","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1046\/j.1365-2249.2001.01391.x","article-title":"Increase of chemokine interferon-inducible protein-10 (IP-10) in the serum of patients with autoimmune liver diseases and increase of its mRNA expression in hepatocytes","volume":"123","author":"Nishioji","year":"2001","journal-title":"Clin. Exp. Immunol."},{"key":"2023033100471263200_jlb0360-cit-B19","doi-asserted-by":"crossref","first-page":"5536","DOI":"10.4049\/jimmunol.158.11.5536","article-title":"Expression of IFN-inducible protein-10 in chronic hepatitis","volume":"158","author":"Narumi","year":"1997","journal-title":"J. Immunol."},{"key":"2023033100471263200_jlb0360-cit-B20","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/0168-8278(91)90084-O","article-title":"Classification of chronic viral hepatitis: a need for reassessment","volume":"13","author":"Scheuer","year":"1991","journal-title":"J. Hepatol."},{"key":"2023033100471263200_jlb0360-cit-B21","first-page":"605","article-title":"Quantitative immunohistologic assessment of lymphocyte populations in the pulmonary inflammatory response to intratracheal silica","volume":"135","author":"Kumar","year":"1989","journal-title":"Am. J. Pathol."},{"key":"2023033100471263200_jlb0360-cit-B22","first-page":"63","article-title":"Stereological Methods","author":"Weibel","year":"1979"},{"key":"2023033100471263200_jlb0360-cit-B23","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s004030050314","article-title":"Chemokine IP-10 expression in cultured human keratinocytes","volume":"290","author":"Boorsma","year":"1998","journal-title":"Arch. Dermatol. Res."},{"key":"2023033100471263200_jlb0360-cit-B24","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/S0168-8278(02)00424-5","article-title":"The presence of an intrahepatic cytotoxic response is associated with low viral load in patients with chronic hepatitis C virus infection","volume":"38","author":"Freeman","year":"2002","journal-title":"J. Hepatol."},{"key":"2023033100471263200_jlb0360-cit-B25","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1097\/00042737-199705000-00015","article-title":"In-situ immunophenotyping study of hepatic-infiltrating cytotoxic cells in chronic active hepatitis C","volume":"9","author":"Fiore","year":"1997","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"2023033100471263200_jlb0360-cit-B26","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/S0168-8278(98)80134-7","article-title":"Histological grading and staging in chronic hepatitis: clinical applications and problems","volume":"29","author":"Hubscher","year":"1998","journal-title":"J. Hepatol."},{"key":"2023033100471263200_jlb0360-cit-B27","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/hep.510310136","article-title":"Grading and staging the histopathological lesions of chronic hepatitis: the Knodell histology activity index and beyond","volume":"31","author":"Brunt","year":"2000","journal-title":"Hepatology"},{"key":"2023033100471263200_jlb0360-cit-B28","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1136\/jcp.49.12.998","article-title":"Histological features predictive of liver fibrosis in chronic hepatitis C infection","volume":"49","author":"Paradis","year":"1996","journal-title":"J. Clin. Pathol."},{"key":"2023033100471263200_jlb0360-cit-B29","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/hep.510240201","article-title":"An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group","volume":"24","author":"Bedossa","year":"1996","journal-title":"Hepatology"},{"key":"2023033100471263200_jlb0360-cit-B30","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/S0167-5699(98)01346-2","article-title":"Chemokines and chemokine receptors in T-cell priming and Th1\/Th2-mediated responses","volume":"19","author":"Sallusto","year":"1998","journal-title":"Immunol. Today"},{"key":"2023033100471263200_jlb0360-cit-B31","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1084\/jem.187.6.875","article-title":"Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes","volume":"187","author":"Sallusto","year":"1998","journal-title":"J. Exp. Med."},{"key":"2023033100471263200_jlb0360-cit-B32","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1084\/jem.177.6.1809","article-title":"Recombinant human interferon-inducible protein 10 is a chemoattractant for human monocytes and T lymphocytes and promotes T cell adhesion to endothelial cells","volume":"177","author":"Taub","year":"1993","journal-title":"J. Exp. Med."},{"key":"2023033100471263200_jlb0360-cit-B33","doi-asserted-by":"crossref","first-page":"3877","DOI":"10.4049\/jimmunol.155.8.3877","article-title":"Alpha and beta chemokines induce NK cell migration and enhance NK-mediated cytolysis","volume":"155","author":"Taub","year":"1995","journal-title":"J. Immunol."},{"key":"2023033100471263200_jlb0360-cit-B34","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1126\/science.1058867","article-title":"Preferential localization of effector memory cells in nonlymphoid tissue","volume":"291","author":"Masopust","year":"2001","journal-title":"Science"},{"key":"2023033100471263200_jlb0360-cit-B35","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/35065111","article-title":"Visualising the generation of memory CD4 T cells in the whole body","volume":"410","author":"Reinhardt","year":"2001","journal-title":"Nature"},{"key":"2023033100471263200_jlb0360-cit-B36","doi-asserted-by":"crossref","first-page":"4511","DOI":"10.4049\/jimmunol.157.10.4511","article-title":"Genes for chemokines MuMig and Crg-2 are induced in protozoan and viral infections in response to IFN-gamma with patterns of tissue expression that suggest nonredundant roles in vivo","volume":"157","author":"Amichay","year":"1996","journal-title":"J. Immunol."},{"key":"2023033100471263200_jlb0360-cit-B37","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/hep.510310225","article-title":"The ratio of ELR+ to ELR\u2013 CXC chemokines affects the lung and liver injury following hepatic ischemia\/reperfusion in the rat","volume":"31","author":"Colletti","year":"2000","journal-title":"Hepatology"},{"key":"2023033100471263200_jlb0360-cit-B38","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1084\/jem.182.1.219","article-title":"The IP-10 chemokine binds to a specific cell surface heparan sulfate site shared with platelet factor 4 and inhibits endothelial cell proliferation","volume":"182","author":"Luster","year":"1995","journal-title":"J. Exp. Med."},{"key":"2023033100471263200_jlb0360-cit-B39","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1172\/JCI9775","article-title":"Cell cycledependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity","volume":"107","author":"Romagnani","year":"2001","journal-title":"J. Clin. Invest."},{"key":"2023033100471263200_jlb0360-cit-B40","doi-asserted-by":"crossref","first-page":"9214","DOI":"10.1128\/JVI.74.19.9214-9221.2000","article-title":"Induction of the chemokines interleukin-8 and IP-10 by human immunodeficiency virus type 1 tat in astrocytes","volume":"74","author":"Kutsch","year":"2000","journal-title":"J. Virol."},{"key":"2023033100471263200_jlb0360-cit-B41","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/S0165-5728(97)00070-2","article-title":"Induction of IP-10 chemokine promoter by measles virus: comparison with interferon-gamma shows the use of the same response element but with differential DNA-protein binding profiles","volume":"77","author":"Nazar","year":"1997","journal-title":"J. Neuroimmunol."},{"key":"2023033100471263200_jlb0360-cit-B42","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1002\/hep.510280240","article-title":"Detection of widespread hepatocyte infection in chronic hepatitis C","volume":"28","author":"Agnello","year":"1998","journal-title":"Hepatology"}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1189%2Fjlb.0303093","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/74\/3\/360\/49658331\/jlb0360.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/74\/3\/360\/49658331\/jlb0360.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T02:00:11Z","timestamp":1680228011000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/74\/3\/360\/6976393"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,6,16]]},"references-count":42,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2003,6,16]]},"published-print":{"date-parts":[[2003,9,1]]}},"URL":"https:\/\/doi.org\/10.1189\/jlb.0303093","relation":{},"ISSN":["0741-5400","1938-3673"],"issn-type":[{"value":"0741-5400","type":"print"},{"value":"1938-3673","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2003,9]]},"published":{"date-parts":[[2003,6,16]]}}}