{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T15:15:11Z","timestamp":1786374911712,"version":"build-2736575974"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI161014"],"award-info":[{"award-number":["R01AI161014"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Human immunodeficiency virus (HIV) persists despite antiretroviral therapy because long-lived viral reservoirs are not eliminated, and ongoing or rebound infection contributes to progressive loss of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T helper cells. Natural killer (NK) cells can acquire adaptive, antigen-experienced functions, including recall responses to HIV envelope protein, suggesting that defined NK-cell subsets may be therapeutically useful against HIV. Because HIV-responsive adaptive NK-cell activity is enriched among CXC chemokine receptor 6-positive (CXCR6\n                    <jats:sup>+<\/jats:sup>\n                    ) NK cells, we tested whether CXCR6\n                    <jats:sup>+<\/jats:sup>\n                    NK cells provide enhanced antiviral activity and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell protection compared with CXCR6\n                    <jats:sup>\u2212<\/jats:sup>\n                    NK cells. In co-cultures with HIV-infected primary CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, PBMC-derived CXCR6\n                    <jats:sup>+<\/jats:sup>\n                    and CXCR6\n                    <jats:sup>\u2212<\/jats:sup>\n                    NK cells both reduced viral replication, but CXCR6\n                    <jats:sup>+<\/jats:sup>\n                    NK cells mediated significantly greater suppression. In HIV-infected humanized mice, weekly infusion of expanded PBMC-derived NK cells lowered plasma viral burden, with CXCR6\n                    <jats:sup>+<\/jats:sup>\n                    NK cells providing stronger preservation of circulating CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells and significant preservation of splenic CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. HIV-Env vaccination further enriched NK cells with enhanced therapeutic activity. CXCR6\n                    <jats:sup>+<\/jats:sup>\n                    NK cells derived from HIV-Env\u2013vaccinated humanized mice produced the strongest suppression of HIV replication and restored CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell frequencies in blood and spleen to levels comparable to uninfected controls. Together, these findings identify CXCR6\n                    <jats:sup>+<\/jats:sup>\n                    NK cells as an HIV-responsive adaptive NK-cell subset that combines antiviral activity with preservation of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell immunity\n                    <jats:italic>in vivo<\/jats:italic>\n                    . These data support further development of CXCR6\n                    <jats:sup>+<\/jats:sup>\n                    NK-cell therapy as a vaccine-informed cellular immunotherapy strategy for HIV.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1888755","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T14:25:31Z","timestamp":1786371931000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CXCR6+ natural killer cell immunotherapy preserves CD4+ T helper cells in humanized mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Naushad","family":"Khan","sequence":"first","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine","place":["Farmington, CT, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla","family":"Frank","sequence":"additional","affiliation":[{"name":"Department of Immunology & Microbiology, The Scripps Research Institute","place":["La Jolla, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Paust","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine","place":["Farmington, CT, United States"]},{"name":"Department of Immunology & Microbiology, The Scripps Research Institute","place":["La Jolla, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"B1","unstructured":"HIV statistics, globally and by WHO region, July 2026"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.24.13193","article-title":"Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy","volume":"94","author":"Chun","year":"1997","journal-title":"Proc Natl Acad Sci USA"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2015.10","article-title":"The multifaceted 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