Circulating Angiogenic and Senescent T Lymphocytes in Ageing and Frailty.

Background: There is a need to identify vascular and geroscience-relevant markers and mediators that can physiologically link ageing to vascular disease. There is evidence of specific T cell subsets, all influenced by age, that exert positive and negative effects on vascular health. CD31+, termed angiogenic T cells, have been linked to vascular repair whereas CD28null, termed senescent T cells, display pro-inflammatory and cytotoxic effector functions.

Objective: This study sought to determine the combined influence of increasing age and frailty status on these circulating CD31+ and CD28null T cell subsets.

Methods: This cross-sectional study recruited four different cohorts of men and women; young (20-30 years, n=22), older (65-75 years, n=17), robust non-frail (76+ years, n=17), and frail (76+ years, n=15) adults. Frailty was determined using the Fried Frailty method. T cell subsets were determined by whole blood flow cytometry based on the expression of CD3, CD4, CD8, CD31 and CD28. Cognitive impairment (CI) was measured via the Montreal Cognitive Assessment test.

Results: Whether expressed as circulating counts or as a % of total T cells, there was a progressive decrease (p<0.05) in CD31+ T cells with increasing age but paradoxically higher values (p<0.05) in the frail compared to the robust non-frail group. These changes were similar in the CD4+ and CD8+ fractions. CD28null T cells were considerably higher (p<0.05) in the frail compared to the robust non-frail group, including in the CD8+ (47% vs 29%, p<0.05) and CD4+ (4% vs 1%, p<0.05) fractions. CD28null T cell percentage was also higher (p<0.05) in those with moderate CI compared to mild CI and normal function.

Conclusion: CD8+CD28null T cells are considerably elevated in frailty and with cognitive impairment and may serve as a useful target for intervention. Currently, the utility of CD31+ T cells as an ageing biomarker may be confined to healthy ageing cohorts.