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Extracellular Vesicles (EVs) are key carriers of immunomodulatory signals and V\u03b42-derived EVs (V\u03b42-EVs) exhibit antitumor activity but their role in viral infection remain unclear. The aim of this study was to investigate the direct and immunomodulatory antiviral functions of V\u03b42-EVs in healthy subjects and HSCT patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The direct antiviral activity of V\u03b42-EVs were tested in vitro using a model of Cytomegalovirus (CMV) replication. The immunomodulatory antiviral activities of V\u03b42-EVs were evaluated in both healthy donors and HSCT recipients by functional immunological assays (cytokine release and proliferation capability of virus-specific T cells). Finally, their molecular cargo was characterized through miRNA sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our findings reveal that V\u03b42-EVs efficiently inhibit CMV replication, reducing the frequency of CMV-infected fibroblast cells. Moreover, V\u03b42-EVs are taken up by myeloid cells and were able to activate antigen-presenting cells, leading to an increased frequency of CMV-specific T cells, as measured by IFN-\u03b3 production. Accordingly, V\u03b42-EVs enhanced the proliferation of CMV-specific T-cell clones in HSCT pediatric recipients. Finally, the analysis of miRNA content in V\u03b42-EVs highlighted the enrichment of miRNAs that target genes regulating critical antiviral response processes such as SOCS1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Altogether, this study provides new insights into the antiviral functions of V\u03b42-EVs and underscores their translational therapeutic potential as modulators of antiviral immunity in immunocompromised settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-026-08062-9","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T16:14:59Z","timestamp":1775837699000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracellular vesicles from activated V\u03b42 T cells inhibit viral replication and enhance adaptive antiviral immunity"],"prefix":"10.1186","volume":"24","author":[{"given":"Veronica","family":"Bordoni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Guarracino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Marocco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Quattrocchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Lorusso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Minutolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Garbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marsha","family":"Pellegrino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Vinci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Matteucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria","family":"Pagliara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Galaverna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Merli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Battistelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Locatelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5252-0927","authenticated-orcid":false,"given":"Chiara","family":"Agrati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"8062_CR1","doi-asserted-by":"crossref","unstructured":"Hayday AC. \u03b3\u03b4 T Cell update: adaptate orchestrators of immune surveillance. 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