{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T02:15:24Z","timestamp":1789265724877,"version":"build-2803163510"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Early antiretroviral therapy (ART) is essential for controlling HIV-1 replication and boosting immune function. \u03b3\u03b4 T cells, as a vital component of the innate immune system, are implicated in the antiviral response. However, their immunological profile during acute HIV-1 infection and the early stages of ART remains unclear. This study aimed to delineate the immunological landscape of \u03b3\u03b4 T cells in individuals with acute HIV-1 infection undergoing early ART. We enrolled 65 participants who initiated ART immediately post-diagnosis and assessed the phenotypes and functions of \u03b3\u03b4 T cells using flow cytometry. We demonstrated that early ART significantly increased the frequency of V\u03b42 T cells, while the V\u03b41 T cell frequency remained stable and showed an inverse relationship with CD4<jats:sup>+<\/jats:sup> T cell counts after ART. Early ART normalized the activation and PD-1 expression in V\u03b41 and V\u03b42 T cells, aligning with healthy controls (HCs) levels. Nevertheless, the proliferation of these cells, particularly within the PD-1<jats:sup>+<\/jats:sup> subset, remains elevated post-ART. We also noted a reduction in perforin secretion in PD-1<jats:sup>+<\/jats:sup> V\u03b41 and V\u03b42 T cells of people living with HIV (PLWH). Furthermore, V\u03b41 T cells were identified as the predominant regulatory T cells, with TGF-\u03b2 production and co-expression of CD127 and CXCR4, negatively correlated with CD8<jats:sup>+<\/jats:sup> T cell activation. Our study elucidates the dynamic immunological characteristics of \u03b3\u03b4 T cells in acute HIV-1 infection and early ART, contributing to the understanding of their role in HIV-1 pathogenesis and the potential for \u03b3\u03b4 T cell-based immunotherapeutic strategies.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1554916","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T04:11:10Z","timestamp":1746677470000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Dynamics and immunological signature of \u03b3\u03b4 T cells following antiretroviral therapy initiation in acute HIV-1 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