{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T07:43:47Z","timestamp":1790322227900,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,5,26]],"date-time":"2019-05-26T00:00:00Z","timestamp":1558828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["Intramural funds"],"award-info":[{"award-number":["Intramural funds"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Immune dysfunction is a hallmark of chronic HCV infection and viral clearance with direct antivirals recover some of these immune defects. TCRV\u03b39V\u03b42 T\u2010cell dysfunction in treated HCV patients however is not well studied and was the subject of this investigation. Peripheral blood cells from patients who had achieved sustained virologic response (SVR) or those who had relapsed after interferon\u2010free therapy were phenotyped using flow cytometry. Functional potential of V\u03b39V\u03b42 T cells was tested by measuring proliferation in response to aminobisphosphonate zoledronic acid, and cytotoxicity against HepG2 hepatoma cell line. TCR sequencing was performed to analyse impact of HCV infection on V\u03b42 T\u2010cell repertoire. V\u03b39V\u03b42 cells from patients were activated and therapy resulted in reduction of CD38 expression on these cells in SVR group. Relapsed patients had V\u03b42 cells with persistently activated and terminally differentiated cytotoxic phenotype (CD38<jats:sup>+<\/jats:sup>CD45RA<jats:sup>+<\/jats:sup>CD27<jats:sup>\u2212<\/jats:sup>CD107a<jats:sup>+<\/jats:sup>). Irrespective of outcome with therapy, majority of patients had persistently poor V\u03b42 T\u2010cell proliferative response to zoledronate along with lower expression of CD56, which identifies anti\u2010tumour cytotoxic subset, relative to healthy controls. There was no association between the number of antigen reactive V\u03b32\u2010J\u03b31.2 TCR rearrangements at baseline and levels of proliferation indicating nonresponse to zoledronate is not due to depletion of phosphoantigen responding chains. Thus, HCV infection results in circulating V\u03b39V\u03b42 T cells with a phenotype equipped for immediate effector function but poor cytokine response and expansion in response to antigen, a functional defect that may have implications for susceptibility for carcinogenesis despite HCV cure.<\/jats:p>","DOI":"10.1111\/jvh.13121","type":"journal-article","created":{"date-parts":[[2019,5,10]],"date-time":"2019-05-10T06:38:26Z","timestamp":1557470306000},"page":"1105-1116","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Persistent gamma delta T\u2010cell dysfunction in chronic HCV infection despite direct\u2010acting antiviral therapy induced cure"],"prefix":"10.1111","volume":"26","author":[{"given":"Alip","family":"Ghosh","sequence":"first","affiliation":[{"name":"Institute of Human Virology University of Maryland School of Medicine Baltimore 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