{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T04:32:31Z","timestamp":1788582751588,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T00:00:00Z","timestamp":1568851200000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT2015\u20102694"],"award-info":[{"award-number":["PICT2015\u20102694"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT2013\/02229"],"award-info":[{"award-number":["PICT2013\/02229"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Intern AIDS Soc"],"published-print":{"date-parts":[[2019,9]]},"abstract":"Abstract<\/jats:title>Introduction<\/jats:title>HIV<\/jats:styled-content> worsens HCV<\/jats:styled-content>\u2010related liver disease by accelerating fibrosis progression; however, progression rates are extremely variable among HIV<\/jats:styled-content>\/HCV<\/jats:styled-content>\u2010coinfected individuals. NK<\/jats:styled-content> cells are associated with modulation of liver fibrosis and are profoundly altered during HCV<\/jats:styled-content> and HIV<\/jats:styled-content> infections. CD<\/jats:styled-content>4+<\/jats:sup> T\u2010cells modulate NK<\/jats:styled-content> cell function, and are also affected by HIV<\/jats:styled-content> infection. Here, we aim to characterize the association of hepatic fibrosis with both the phenotype and function of peripheral NK<\/jats:styled-content> cells and their regulation by CD<\/jats:styled-content>4+<\/jats:sup> T\u2010cells, in HIV<\/jats:styled-content>\/HCV<\/jats:styled-content>\u2010coinfected individuals.<\/jats:p><\/jats:sec>Methods<\/jats:title>Thirty\u2010four HIV<\/jats:styled-content>\/HCV<\/jats:styled-content>\u2010coinfected individuals with minimal (n\u00a0=\u00a016) and advanced (n\u00a0=\u00a018) fibrosis (METAVIR<\/jats:styled-content> F0\/F1 and F4 scores respectively) and 20 healthy volunteers were enrolled. PBMC<\/jats:styled-content> were obtained from peripheral blood samples and NK<\/jats:styled-content> and CD<\/jats:styled-content>4+<\/jats:sup> T\u2010cells were isolated and analysed. NK<\/jats:styled-content> cell phenotype (CD<\/jats:styled-content>25, CD<\/jats:styled-content>69, Nkp46, NKG<\/jats:styled-content>2D, PD<\/jats:styled-content>\u20101), degranulation (CD<\/jats:styled-content>107a) and IFN<\/jats:styled-content>\u2010\u03b3 and TNF<\/jats:styled-content>\u2010\u03b1 production, as well as CD<\/jats:styled-content>4+<\/jats:sup> T\u2010cell activation (CD<\/jats:styled-content>69, CD<\/jats:styled-content>25 and CD<\/jats:styled-content>38) were measured by flow cytometry. CD<\/jats:styled-content>4+<\/jats:sup> T\u2010cell conditioned medium (CM<\/jats:styled-content>) derived from F0\/F1 or F4 individuals was assessed for IL<\/jats:styled-content>\u20102 levels by ELISA<\/jats:styled-content>. Modulation of NK<\/jats:styled-content> cell functionality by these CM<\/jats:styled-content>s was also analysed.<\/jats:p><\/jats:sec>Results<\/jats:title>When comparing to NK<\/jats:styled-content> cells from individuals with minimal fibrosis, degranulation and cytokine secretion by NK<\/jats:styled-content> cells from subjects with F4 scores was significantly impaired, while PD<\/jats:styled-content>\u20101 expression was augmented. On the one hand, neither the expression of activation markers nor IL<\/jats:styled-content>\u20102 secretion was distinctly induced in CD<\/jats:styled-content>4+<\/jats:sup> T\u2010cells from subjects with F0\/F1 or F4 METAVIR<\/jats:styled-content> scores. Finally, NK<\/jats:styled-content> cell degranulation and cytokine secretion were not differentially modulated by CD<\/jats:styled-content>4+<\/jats:sup> T\u2010cell CM<\/jats:styled-content>, whether CD<\/jats:styled-content>4+<\/jats:sup> T\u2010cells derived from subjects with minimal or advanced fibrosis.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Low levels of NK<\/jats:styled-content> and CD<\/jats:styled-content>4+<\/jats:sup> T\u2010cells in HIV<\/jats:styled-content>\/HCV<\/jats:styled-content>\u2010coinfected individuals with advanced liver fibrosis have been previously described. Here, we show that advanced liver fibrosis in coinfected individuals is associated to a defective function of NK<\/jats:styled-content> cells and an increased expression of the exhaustion\/senescence marker PD<\/jats:styled-content>\u20101. This NK<\/jats:styled-content> signature could not be attributed to changes in the ability of CD<\/jats:styled-content>4+<\/jats:sup> T\u2010cells to modulate NK<\/jats:styled-content> cell function.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jia2.25375","type":"journal-article","created":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T12:44:07Z","timestamp":1568897047000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Liver cirrhosis in HIV<\/scp>\/HCV<\/scp>\u2010coinfected individuals is related to NK<\/scp> cell dysfunction and exhaustion, but not to an impaired NK<\/scp> cell modulation by CD<\/scp>4+<\/sup> T\u2010cells"],"prefix":"10.1002","volume":"22","author":[{"given":"Mar\u00eda L","family":"Polo","sequence":"first","affiliation":[{"name":"CONICET\u2010Universidad de Buenos Aires Instituto de Investigaciones Biom\u00e9dicas en Retrovirus y Sida (INBIRS) Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanina A","family":"Ghiglione","sequence":"additional","affiliation":[{"name":"CONICET\u2010Universidad de Buenos Aires Instituto de Investigaciones Biom\u00e9dicas en Retrovirus y Sida (INBIRS) Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimena P","family":"Salido","sequence":"additional","affiliation":[{"name":"CONICET\u2010Universidad de Buenos Aires Instituto de Investigaciones Biom\u00e9dicas en Retrovirus y Sida (INBIRS) Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Urioste","sequence":"additional","affiliation":[{"name":"CONICET\u2010Universidad de Buenos Aires Instituto de Investigaciones Biom\u00e9dicas en Retrovirus y Sida (INBIRS) Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Poblete","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit Hospital General de Agudos \u201cDr. JA Fern\u00e1ndez\u201d Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia E","family":"Sisto","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit Hospital General de Agudos \u201cDr. JA Fern\u00e1ndez\u201d Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Martinez","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit Hospital General de Agudos \u201cDr. JA Fern\u00e1ndez\u201d Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda J","family":"Rol\u00f3n","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit Hospital General de Agudos \u201cDr. JA Fern\u00e1ndez\u201d Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego S","family":"Ojeda","sequence":"additional","affiliation":[{"name":"CONICET\u2010Universidad de Buenos Aires Instituto de Investigaciones Biom\u00e9dicas en Retrovirus y Sida (INBIRS) Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro E","family":"Cahn","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Hu\u00e9sped Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela J","family":"Turk","sequence":"additional","affiliation":[{"name":"CONICET\u2010Universidad de Buenos Aires Instituto de Investigaciones Biom\u00e9dicas en Retrovirus y Sida (INBIRS) Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5690-9454","authenticated-orcid":false,"given":"Natalia L","family":"Laufer","sequence":"additional","affiliation":[{"name":"CONICET\u2010Universidad de Buenos Aires Instituto de Investigaciones Biom\u00e9dicas en Retrovirus y Sida (INBIRS) Buenos Aires Argentina"},{"name":"Infectious Diseases Unit Hospital General de Agudos \u201cDr. JA Fern\u00e1ndez\u201d Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,19]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"World Health Organization.Global hepatitis 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