CD8+ effector memory and regulatory T cell dynamics predict subclinical atherosclerotic plaque formation in healthy aging.

BACKGROUND: Subclinical atherosclerotic plaque (SAP) develops silently in older adults. 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. METHODS: In a three-year longitudinal study, 49 healthy older adults (63.8 ± 3.8 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. RESULTS: New SAP occurred in 30.3% of those initially plaque-free. At baseline, lower frequencies of CD8+ effector memory (EM) T cells and higher frequencies of CD8+ 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+ 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 VO2peak were linked to new SAP, but immune markers were more robust than metabolic variables or serum cytokines. CONCLUSION: Adaptive immune remodeling follows a phase-dependent pattern in which CD8+ EM reductions and later CD8+ 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.