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We used flow cytometry and Western blot analysis to quantify expression of PVR and its ligands in na\u00efve and effector T cells and used adhesion assays and enzyme-linked immunosorbent assay (ELISA) to assess the impact of PVR on T cell adhesion and cytokine production. Stimulation with phytohemagglutinin P strongly increased DNAM-1 expression and caused a less robust and more variable increase in TIGIT expression. Exposure to PVR-Fc enhanced the CD8+ T cell adhesion to ICAM-1\u2013coated plates in a dose-dependent manner, while exposure to PVR-expressing K32 cells mildly decreased CD8+ T cell interferon \u03b3 release. However, PVR exposure strongly decreased the expression of DNAM-1, TIGIT, and CD96. The reduction of DNAM-1, TIGIT, and CD96 induced by PVR was dominant to the increase caused by T cell receptor signaling. The impact of PVR on their expression was completely abolished by the Q63R and F128R point mutations of PVR, while DNAM-1 was partially rescued by inhibitors of Src and protein kinase C. Additionally, PVR exposure along with T cell receptor signaling promoted the transfer of surface proteins including PVR from K32 cells to CD8+ T cells. This PVR transfer was mediated by the IgV domain of PVR and CD96 on CD8+ T cells and required cellular contact. Our findings collectively demonstrate that PVR engagement has a mild antagonistic effect on interferon \u03b3 production but strongly impacts CD8+ T cell adhesion and protein expression.<\/jats:p>","DOI":"10.1093\/jimmun\/vkae002","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T14:57:36Z","timestamp":1737644256000},"page":"55-71","source":"Crossref","is-referenced-by-count":2,"title":["PVR exposure influences the activation, adhesion, and protein expression of human CD8+ T cells, including the CD96-mediated transfer of PVR"],"prefix":"10.1093","volume":"214","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4912-0375","authenticated-orcid":false,"given":"Xueting","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Connecticut , Storrs, CT,","place":["United 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