{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:05:32Z","timestamp":1792677932138,"version":"4.5.0"},"reference-count":43,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"640","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2022,4,13]]},"abstract":"<jats:p>\n            A better understanding of mechanisms that regulate CD8\n            <jats:sup>+<\/jats:sup>\n            T cell responses to therapeutic vaccines is needed to develop approaches to enhance vaccine efficacy for chronic viral infections and cancers. We show here that NK cell depletion enhanced antigen-specific T cell responses to chimp adenoviral vector (ChAdOx) vaccination in a mouse model of chronic HBV infection (CHB). Probing the mechanism underlying this negative regulation, we observed that CHB drove parallel up-regulation of programmed cell death ligand 1 (PD-L1) on liver-resident NK cells and programmed cell death 1 (PD-1) on intrahepatic T cells. PD-L1\u2013expressing liver-resident NK cells suppressed PD-1\n            <jats:sup>hi<\/jats:sup>\n            CD8\n            <jats:sup>+<\/jats:sup>\n            T cells enriched within the HBV-specific response to therapeutic vaccination. Cytokine activation of NK cells also induced PD-L1, and combining cytokine activation with PD-L1 blockade resulted in conversion of NK cells into efficient helpers that boosted HBV-specific CD8\n            <jats:sup>+<\/jats:sup>\n            T cell responses to therapeutic vaccination in mice and to chronic infection in humans. Our findings delineate an immunotherapeutic combination that can boost the response to therapeutic vaccination in CHB and highlight the broader importance of PD-L1\u2013dependent regulation of T cells by cytokine-activated NK cells.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.abi4670","type":"journal-article","created":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T17:56:07Z","timestamp":1649872567000},"source":"Crossref","is-referenced-by-count":49,"title":["NK cells limit therapeutic vaccine\u2013induced CD8\n            <sup>+<\/sup>\n            T cell immunity in a PD-L1\u2013dependent manner"],"prefix":"10.1126","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1961-0189","authenticated-orcid":true,"given":"Mariana O.","family":"Diniz","sequence":"first","affiliation":[{"name":"Division of Infection and Immunity and Institute of Immunity and Transplantation, UCL, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2525-3114","authenticated-orcid":true,"given":"Anna","family":"Schurich","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity and Institute of Immunity and Transplantation, UCL, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senthil K.","family":"Chinnakannan","sequence":"additional","affiliation":[{"name":"Peter Medawar Building for Pathogen Research, Nuffield Dept of Medicine, University of Oxford, Oxford, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Duriez","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity and Institute of Immunity and Transplantation, UCL, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin A.","family":"Stegmann","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity and Institute of Immunity and Transplantation, UCL, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Davies","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity and Institute of Immunity and Transplantation, UCL, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8849-218X","authenticated-orcid":true,"given":"Stephanie","family":"Kucykowicz","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity and Institute of Immunity and Transplantation, UCL, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8235-0431","authenticated-orcid":true,"given":"Kornelija","family":"Suveizdyte","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity and Institute of Immunity and Transplantation, UCL, London, 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