{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T20:24:21Z","timestamp":1784838261257,"version":"3.55.0"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:sec>\n            <jats:title>INTRODUCTION:<\/jats:title>\n            <jats:p>\n              Viral infections have been associated with the progression of atherosclerosis and CD8\n              <jats:sup>+<\/jats:sup>\n              T-cells directed against common viruses, such as influenza, Epstein-Barr virus, and cytomegalovirus, have been detected inside human atherosclerotic lesions. These virus-specific CD8\n              <jats:sup>+<\/jats:sup>\n              T-cells have been hypothesized to contribute to the development of atherosclerosis; however, whether they affect disease progression directly remains unclear. In this study, we aimed to characterize the activation status of virus-specific CD8\n              <jats:sup>+<\/jats:sup>\n              T-cells in the atherosclerotic lesion.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              The presence, clonality, tissue enrichment, and phenotype of virus-associated CD8\n              <jats:sup>+<\/jats:sup>\n              T-cells in atherosclerotic lesions were assessed by exploiting bulk T-cell receptor-\u03b2 sequencing and single-cell T-cell receptor (\u03b1 and \u03b2) sequencing datasets on human endarterectomy samples and patient-matched blood samples. To investigate if virus-specific CD8\n              <jats:sup>+<\/jats:sup>\n              T-cells can be activated through T-cell receptor stimulation in the atherosclerotic lesion, the immunopeptidome of human plaques was determined.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Virus-associated CD8\n              <jats:sup>+<\/jats:sup>\n              T-cells accumulated more in the atherosclerotic lesion (mean=2.0%), compared with patient-matched blood samples (mean=1.4%;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.05), and were more clonally expanded and tissue enriched in the atherosclerotic lesion in comparison with nonassociated CD8\n              <jats:sup>+<\/jats:sup>\n              T-cells from the lesion. Single-cell T-cell receptor sequencing and flow cytometry revealed that these virus-associated CD8\n              <jats:sup>+<\/jats:sup>\n              T-cells were phenotypically highly similar to other CD8\n              <jats:sup>+<\/jats:sup>\n              T-cells in the lesion and that both exhibited a more activated phenotype compared with circulating T-cells. Interestingly, virus-associated CD8\n              <jats:sup>+<\/jats:sup>\n              T-cells are unlikely to be activated through antigen-specific interactions in the atherosclerotic lesion, as no virus-derived peptides were detected on HLA-I in the lesion.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>\n              This study suggests that virus-specific CD8\n              <jats:sup>+<\/jats:sup>\n              T-cells are tissue enriched in atherosclerotic lesions; however, their potential contribution to inflammation may involve antigen-independent mechanisms.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.123.320539","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T09:00:32Z","timestamp":1711011632000},"page":"1302-1314","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Virus-Associated CD8\n            <sup>+<\/sup>\n            T-Cells Are Not Activated Through Antigen-Mediated Interaction Inside Atherosclerotic Lesions"],"prefix":"10.1161","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1000-0253","authenticated-orcid":true,"given":"Maaike J.M.","family":"de Jong","sequence":"first","affiliation":[{"name":"Leiden Academic Centre for Drug Research, Division of BioTherapeutics, Leiden University, the Netherlands (M.J.M.J., F.H.S., M.A.C.D., F.L.V., J.K., I.B., B.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5742-489X","authenticated-orcid":true,"given":"Frank 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I.B., B.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6398-7750","authenticated-orcid":true,"given":"George M.C.","family":"Janssen","sequence":"additional","affiliation":[{"name":"Department of Immunology, Leiden University Medical Centre, Center for Proteomics and Metabolomics, the Netherlands (G.M.C.J., P.v.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0051-9836","authenticated-orcid":true,"given":"Judith A.H.M.","family":"Peeters","sequence":"additional","affiliation":[{"name":"Department of Surgery, Haaglanden Medical Center \u2013 location Westeinde, Lijnbaan, The Hague, the Netherlands (J.A.H.M.P., L.G., A.W., H.J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Goncalves","sequence":"additional","affiliation":[{"name":"Department of Surgery, Haaglanden Medical Center \u2013 location Westeinde, Lijnbaan, The Hague, the Netherlands 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