CD31 ⁺ T-cells express greater VEGF-A and CXCR4 levels than CD31 ^- counterparts with VEGF-A expression exacerbated with advancing age

Abstract CD31 + T-cells reportedly possess angiogenic properties. These cells have recently been termed angiogenic T-cells (T ANG ). Advancing age is associated with altered circulating T-cell phenotypes, including T ANG , and reduced angiogenesis. We examined various T ANG subsets (CD3 + , CD4 + , CD8 + ), and their VEGF-A intracellular content in young (n=16, 18-30 years) and older (n=16, 50-65 years) male adults using flow cytometry. Cardiorespiratory fitness ( V̇ O 2 max) was quantified in all participants using a graded cycling ergometry test to volitional exhaustion. Resting blood samples were collected to measure circulating IL-6 and cytomegalovirus serostatus. CD31 + T-cells (T ANG ) contained more VEGF-A than CD31 - T-cells (CD31 + : 9374 ± 8587 AU vs CD31 - : 8722 ± 8149 AU, p = 0.021) which was also exhibited in CD4 + and CD8 + subsets. Older adults possessed fewer CD4 + T ANG cells as a proportion of total CD4 + T-cells than younger adults (young: 35 ± 11%; older: 24 ± 9%, p = 0.004), and CD3 + and CD4 + T ANG subsets from older adults exhibited higher VEGF-A levels than younger adults (CD3 + CD31 + : young: 6081 ± 4001 AU; older: 13426 ± 10945 AU, p = 0.019; CD4 + CD31 + : young: 6373 ± 3972 AU; older: 15660 ± 12829 AU, p = 0.011). T ANG cells were not associated with circulating IL-6, and T ANG VEGF-A content was not associated with V̇ O 2 max. Advancing age is associated with a pathological T ANG phenotype, which may contribute to age-related inflammation and warrants further investigation as a potential therapeutic target.