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Biological changes that predict plaque formation are not well defined. We examined whether circulating immunological, metabolic, and functional measures identify vascular vulnerability before clinical disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a three-year longitudinal study, 49 healthy older adults (63.8\u2009\u00b1\u20093.8 years) underwent carotid ultrasound, T cell phenotyping, serum protein profiling, body composition assessment, and fitness testing at baseline and follow-up. At follow-up, participants were classified as no SAP, new SAP or persistent SAP. We analyzed baseline determinants and within-person changes to predict incident plaque formation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      New SAP occurred in 30.3% of those initially plaque-free. At baseline, lower frequencies of CD8\n                      <jats:sup>+<\/jats:sup>\n                      effector memory (EM) T cells and higher frequencies of CD8\n                      <jats:sup>+<\/jats:sup>\n                      effector memory re-expressing CD45RA (EMRA) T cells and regulatory T cells (Tregs) were associated with higher odds of new SAP. Over time, expansion of CD8\n                      <jats:sup>+<\/jats:sup>\n                      EM T cells was the most consistently associated independent variable of new SAP, accompanied by declines in Tregs and in the Treg\/Teff ratio. Vascular cell adhesion molecule-1 (VCAM-1) at baseline was an additional independent predictor. Increases in visceral fat and declines in VO\n                      <jats:sub>2<\/jats:sub>\n                      peak were linked to new SAP, but immune markers were more robust than metabolic variables or serum cytokines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Adaptive immune remodeling follows a phase-dependent pattern in which CD8\n                      <jats:sup>+<\/jats:sup>\n                      EM reductions and later CD8\n                      <jats:sup>+<\/jats:sup>\n                      EM expansion with Treg decline signal emerging vascular vulnerability. These immune signatures, together with VCAM-1, may help characterize vascular vulnerability during the subclinical phase of plaque development.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12979-026-00588-2","type":"journal-article","created":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T04:34:36Z","timestamp":1786768476000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CD8+ effector memory and regulatory T cell dynamics predict subclinical atherosclerotic plaque formation in healthy aging"],"prefix":"10.1186","volume":"23","author":[{"given":"Christopher","family":"Weyh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Gr\u00f6\u00dfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciele Guerra","family":"Minuzzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Frech","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Gebhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja","family":"Nolte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa Regine","family":"Dombrowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"B\u00f6ttrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela Andrea","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natascha","family":"Sommer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Ringseis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Eder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Sossalla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1506-8254","authenticated-orcid":false,"given":"Karsten","family":"Kr\u00fcger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,15]]},"reference":[{"key":"588_CR1","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1177\/2047487314566999","volume":"23","author":"KA Groenewegen","year":"2016","unstructured":"Groenewegen KA, den Ruijter HM, Pasterkamp G, Polak JF, Bots ML, Peters SA. 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