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RESEARCH PAPER / 2026-04-01

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

Stephen, L., Wright, G., Muggeridge, D. J., Leggate, M., Chandrakumar, V., Ross, M. D.

Heriot-Watt UniversityHeriot-Watt University · biorxiv

Abstract

CD31+ T-cells reportedly possess angiogenic properties. These cells have recently been termed angiogenic T-cells (TANG). Advancing age is associated with altered circulating T-cell phenotypes, including TANG, and reduced angiogenesis. We examined various TANG subsets (CD3+, CD4+, CD8+), and their VEGF-A intracellular content in young (n=11, 18-30 years) and older (n=13, 50-65 years) male adults using flow cytometry. Cardiorespiratory fitness (VO2max) 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 (TANG) 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+ TANG 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+ TANG 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). TANG cells were not associated with circulating IL-6, and TANG VEGF-A content was not associated with VO2max. Advancing age is associated with a pathological TANG phenotype, which may contribute to age-related inflammation and warrants further investigation as a potential therapeutic target.

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Research summary

Advancing age is associated with a pathological TANG phenotype that may contribute to age-related inflammation. The study investigates the changes in T-cell subsets and their potential role in aging, which aligns with understanding the mechanisms of aging and potential therapeutic targets.

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