{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T03:03:38Z","timestamp":1773803018410,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,8,15]],"date-time":"2013-08-15T00:00:00Z","timestamp":1376524800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100000691","name":"Academy of Medical Sciences","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000691","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Janssen and Gilead"},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["WT091663MA"],"award-info":[{"award-number":["WT091663MA"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Oxford Martin School"},{"name":"NIHR Biomedical Research Centre"},{"name":"NIAID U19 Bio-defense Program","award":["NIH NIAID 1U19AI082630-01"],"award-info":[{"award-number":["NIH NIAID 1U19AI082630-01"]}]},{"DOI":"10.13039\/501100000651","name":"Leukaemia and Lymphoma Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000651","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2014,4]]},"abstract":"Summary<\/jats:title>Coinfection with HIV<\/jats:styled-content> adversely impacts every stage of hepatitis C<\/jats:styled-content> (HCV<\/jats:styled-content>) infection. Liver damage in HCV<\/jats:styled-content> infection results from host antiviral responses rather than direct viral pathogenesis. Despite depressed cellular immunity, coinfected patients show accelerated hepatic fibrosis compared with HCV<\/jats:styled-content> monoinfected patients. This paradox is poorly understood. T<\/jats:styled-content>\u2010regulatory (Treg) cells (CD<\/jats:styled-content>4+ and FOXP<\/jats:styled-content>3+) are hypothesized to limit hepatic damage in HCV<\/jats:styled-content>. Our hypothesis was that reduced frequency of hepatic T<\/jats:styled-content>reg in HIV<\/jats:styled-content>\/HCV<\/jats:styled-content> coinfection compared with HCV<\/jats:styled-content> monoinfection may explain poorer outcomes. We quantified FOXP<\/jats:styled-content>3+, CD<\/jats:styled-content>4+, CD<\/jats:styled-content>8+ and CD<\/jats:styled-content>20+ cells in liver biopsies of 35 male subjects matched by age and ISHAK<\/jats:styled-content> fibrosis score, 12 HIV<\/jats:styled-content> monoinfected, 11 HCV<\/jats:styled-content> monoinfected and 12 HIV<\/jats:styled-content>\/HCV<\/jats:styled-content> coinfected. Cell counts were performed using indirect immunohistochemical staining and light microscopy. HIV<\/jats:styled-content>\/HCV<\/jats:styled-content> coinfected subjects had fewer hepatic FOXP<\/jats:styled-content>3+ (P<\/jats:italic>\u00a0=\u00a00.031) and CD<\/jats:styled-content>4+ cells (P<\/jats:italic>\u00a0=\u00a00.001) than HCV<\/jats:styled-content> monoinfected subjects. Coinfected subjects had more hepatic CD<\/jats:styled-content>8+ cells compared with HCV<\/jats:styled-content> monoinfected (P<\/jats:italic>\u00a0=\u00a00.023), and a lower ratio of FOXP<\/jats:styled-content>3+ to CD<\/jats:styled-content>8+ cells (0.08 vs<\/jats:italic> 0.27, P<\/jats:italic>\u00a0<\u00a00.001). Multivariate analysis showed number of CD<\/jats:styled-content>4+ cells controlled for differences in number of FOXP<\/jats:styled-content>3+ cells. Fewer hepatic FOXP<\/jats:styled-content>3+ and CD<\/jats:styled-content>4+ cells in HIV<\/jats:styled-content>\/HCV<\/jats:styled-content> coinfection compared with HCV<\/jats:styled-content> monoinfection suggests lower T<\/jats:styled-content>reg activity, driven by an overall loss of CD<\/jats:styled-content>4+ cells. Higher number of CD<\/jats:styled-content>8+ cells in HIV<\/jats:styled-content>\/HCV<\/jats:styled-content> coinfection suggests higher cytotoxic activity. This may explain poorer outcomes in HIV<\/jats:styled-content>\/HCV<\/jats:styled-content> coinfected patients and suggests a potential mechanism by which highly active antiretroviral therapy may benefit these patients.<\/jats:p>","DOI":"10.1111\/jvh.12141","type":"journal-article","created":{"date-parts":[[2013,8,15]],"date-time":"2013-08-15T14:34:11Z","timestamp":1376577251000},"page":"251-259","source":"Crossref","is-referenced-by-count":5,"title":["Quantification of hepatic FOXP<\/scp>3+ T<\/scp>\u2010lymphocytes in HIV<\/scp>\/hepatitis C<\/scp> coinfection"],"prefix":"10.1111","volume":"21","author":[{"given":"S. K.","family":"Williams","sequence":"first","affiliation":[{"name":"Brighton and Sussex University Hospitals Brighton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Donaldson","sequence":"additional","affiliation":[{"name":"Brighton and Sussex University Hospitals Brighton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Van der Kleij","sequence":"additional","affiliation":[{"name":"Brighton and Sussex Medical School Brighton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Dixon","sequence":"additional","affiliation":[{"name":"Brighton and Sussex University Hospitals Brighton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Brighton and Sussex University Hospitals Brighton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Tibble","sequence":"additional","affiliation":[{"name":"Brighton and Sussex University Hospitals Brighton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Gilleece","sequence":"additional","affiliation":[{"name":"Brighton and Sussex University Hospitals Brighton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Klenerman","sequence":"additional","affiliation":[{"name":"Peter Medawar Building for Pathogen Research Nuffield Department of Clinical Medicine University of Oxford Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. H.","family":"Banham","sequence":"additional","affiliation":[{"name":"Nuffield Division of Clinical Laboratory Sciences Radcliffe Department of Medicine University of Oxford Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Howard","sequence":"additional","affiliation":[{"name":"Brighton and Sussex University Hospitals Brighton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. 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