Accelerated maturation of antiviral T cell immunity in children living with HIV despite antiretroviral therapy

Accelerated maturation of antiviral T cell immunity in children living with HIV despite antiretroviral therapy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Accelerated maturation of antiviral T cell immunity in children living with HIV despite antiretroviral therapy Annika Karlsson, Anna Olofsson, Marion Humbert, Curtis Cai, Lydia Scharf, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9357619/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Mother-to-child transmission remains the predominant cause of paediatric HIV infection. Despite effective antiretroviral therapy (ART), it remains unclear how paediatric HIV reshapes the development and functional specialization of antiviral T cell immunity beyond HIV-specific responses. Here, we compared antigen-specific memory CD8⁺ and CD4⁺ T cell responses to four common viruses in children (n = 24) and adults living with HIV (n = 40), alongside HIV-negative children (n = 19) and adults (n = 39), matched for cytomegalovirus (CMV) serostatus. Using high-parameter flow cytometry, we show that children living with HIV (CLWH) exhibit a more adult-like memory CD8⁺ T cell compartment, characterized by increased expression of late differentiation markers. CMV- and Epstein–Barr virus (EBV)-specific CD8⁺ T cells displayed enhanced polyfunctionality and cytotoxic potential in CLWH compared with HIV-negative children, whereas responses to acute respiratory viruses were largely preserved. Single-cell RNA sequencing revealed clonal expansion of CMV-specific CD8⁺ T cells and a pro-inflammatory transcriptional bias in antigen-specific CD4⁺ T cells in CLWH. Together, these findings demonstrate that paediatric HIV infection, despite ART, accelerates the maturation and functional specialization of selected antiviral T cell populations, with potential implications for long-term immune health. Health sciences/Medical research/Paediatric research Health sciences/Diseases/Infectious diseases/HIV infections Health sciences/Medical research/Translational research Biological sciences/Immunology/Adaptive immunity/Cellular immunity/Immunological memory Biological sciences/Microbiology/Virology/Virus–host interactions Full Text Additional Declarations There is NO Competing Interest. Supplementary Files RS.pdf Reporting Summary Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9357619","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":624637385,"identity":"54c0965e-9c28-445f-9493-4a231430848a","order_by":0,"name":"Annika 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