{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T08:04:03Z","timestamp":1771315443479,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:00:00Z","timestamp":1764374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:00:00Z","timestamp":1764374400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Despite effective viral suppression, a subpopulation of people living with HIV (PLWH) receiving combination antiretroviral therapy (ART) experience a suboptimal immunological response, failing to restore CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell counts to levels deemed indicative of good immune recovery. Innate immune cell dysregulation, particularly in mucosal\u2010associated invariant T (MAIT) and natural killer (NK) cells, is increasingly recognized as a key contributor to immune reconstitution. However, the dynamic changes, interactive crosstalk, and potential roles of these immune cells in immune reconstitution remain poorly understood. A total of 89 participants were enrolled, including 29 healthy controls and 60 HIV\u2010infected individuals, who were classified as immune responders (IRs, CD4\u2009\u2265\u2009500 cells\/\u00b5L;\n                    <jats:italic>n\u2009<\/jats:italic>\n                    =\u200934) and suboptimal immunological responders (SIRs, CD4\u2009&lt;\u2009500 cells\/\u00b5L;\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200926) on the basis of immune recovery status. Longitudinal flow cytometric analysis was performed to assess the phenotypic changes in MAIT and NK cell subsets in peripheral blood mononuclear cells (PBMCs) before treatment (T0) and after 4 years of ART (T4). Correlation analysis was conducted to explore their associations with CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell recovery. After 4 years of ART, both IRs and SIRs exhibited persistent depletion of total MAIT and invariant natural killer T (iNKT) cells, whereas pretreatment\u2010diminished CD56\n                    <jats:sup>bright<\/jats:sup>\n                    and CD56\n                    <jats:sup>dim<\/jats:sup>\n                    NK cell subsets increased significantly. MAIT cells also underwent phenotypic remodeling in both groups, with decreased CD4\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    and increased CD4\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD8\n                    <jats:sup>\u2212<\/jats:sup>\n                    subsets. Notably, these cell subset proportions and quantitative changes correlated significantly with CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell counts in IRs but not SIRs. In IRs, CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell recovery positively correlated with baseline CD4\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD8\n                    <jats:sup>\u2212<\/jats:sup>\n                    MAIT and CD56\n                    <jats:sup>bright<\/jats:sup>\n                    NK cell numbers, but negatively with baseline CD4\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    MAIT cell numbers. Correlation networks revealed distinct MAIT\u2013NK interactions across ART stages. LASSO models integrating MAIT and NK subsets achieved high predictive accuracy, highlighting the dynamic role of CD4\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    MAIT cells in immune reconstitution. Our study highlights the dynamic correlations between and within MAIT and NK cell subset proportions in PLWH, revealing that phenotypic remodeling rather than absolute cell counts plays a key role in immune reconstitution. CD4\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    MAIT cells show time\u2010dependent predictive shifts, reflecting functional adaptation. These findings identify MAIT and NK subset dynamics as potential biomarkers and therapeutic targets for enhancing immune recovery of PLWH during ART.\n                  <\/jats:p>","DOI":"10.1002\/jmv.70732","type":"journal-article","created":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T12:36:07Z","timestamp":1764419767000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Subset Remodeling of MAIT and NK Cells Correlates With Immune Reconstitution in People Living With HIV Following Four Years of Antiretroviral Therapy"],"prefix":"10.1002","volume":"97","author":[{"given":"Zhuoya","family":"Deng","sequence":"first","affiliation":[{"name":"Beijing Key Laboratory for HIV\/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital Capital Medical University Beijing China"},{"name":"Sino\u2010French Joint Laboratory for HIV\/AIDS Research, Sino\u2010French Joint Laboratory for Research on Humoral Immune Response to HIV Infection, Beijing Youan Hospital Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory for HIV\/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital Capital Medical University Beijing China"},{"name":"Sino\u2010French Joint Laboratory for HIV\/AIDS Research, Sino\u2010French Joint Laboratory for Research on Humoral Immune Response to HIV Infection, Beijing Youan Hospital Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiwei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory for HIV\/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital Capital Medical University Beijing China"},{"name":"Sino\u2010French Joint Laboratory for HIV\/AIDS Research, Sino\u2010French Joint Laboratory for Research on Humoral Immune Response to HIV Infection, Beijing Youan Hospital Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases The First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Immunity and Infectious Diseases, Third People's Hospital of Shenzhen National Clinical Research Center for Infectious Diseases Shenzhen Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongxia","family":"Yan","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory for HIV\/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital Capital Medical University Beijing China"},{"name":"Sino\u2010French Joint Laboratory for HIV\/AIDS Research, Sino\u2010French Joint Laboratory for Research on Humoral Immune Response to HIV Infection, Beijing Youan Hospital Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory for HIV\/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital Capital Medical University Beijing China"},{"name":"Sino\u2010French Joint Laboratory for HIV\/AIDS Research, Sino\u2010French Joint Laboratory for Research on Humoral Immune Response to HIV Infection, Beijing Youan Hospital Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2534-4785","authenticated-orcid":false,"given":"Tong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory for HIV\/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital Capital Medical University Beijing China"},{"name":"Sino\u2010French Joint Laboratory for HIV\/AIDS Research, Sino\u2010French Joint Laboratory for Research on Humoral Immune Response to HIV Infection, Beijing Youan Hospital Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christiane","family":"Moog","sequence":"additional","affiliation":[{"name":"Sino\u2010French Joint Laboratory for HIV\/AIDS Research, Sino\u2010French Joint Laboratory for Research on Humoral Immune Response to HIV Infection, Beijing Youan Hospital Capital Medical University Beijing China"},{"name":"Laboratoire 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Beijing Youan Hospital Capital Medical University Beijing China"},{"name":"Central Laboratory, Beijing Youan Hospital Capital Medical University Beijing China"},{"name":"Scientific and Technological Achievement Transformation Center, Beijing Youan Hospital Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,29]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"World Aids Day Report 2024: Take the Rights Path. 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