Increased proportion of CD8+ CCR5+ Eomes^hiT cells is associated with aortic stiffness in human aging and hypertension

Hypertension is a growing health concern worldwide and is an independent risk factor for the development of cardiovascular disease (CVD) in the aging population. T cells have been implicated to play a role in the development of hypertension and CVD by altering the inflammatory milieu within the blood vessels. More specifically, the chemokine receptor CCR5 facilitates the migration of CD8+ (cytotoxic) T cells to the sites of inflammation in the vascular wall and the transcription factor Eomesodermin (Eomes) is crucial in the differentiation of CD8+ T cells from a naive to memory phenotype which determines the functional state of these CD8+ cells. Expression of Eomes has been shown to be greater in CD8+ T cells with advancing age in mice and humans. Previous studies from our laboratory have shown that CD8+ CCR5+ T cells accumulate in the aorta of old mice and are related to greater large artery stiffening. Also, our preliminary studies using PBMCs from older adults showed that a large proportion of Eomes hi cells were also CCR5 positive. However, whether CD8+ cells expressing both CCR5 and Eomes are associated with large artery stiffness and high blood pressure (BP) in older adults is not known. Therefore, the aim of this study was to determine whether proportions of CD8+ CCR5 Eomes hi T cells are associated with arterial stiffness and BP in humans. We hypothesized that older adults with hypertension would have greater proportions of circulating CD8+ T cells expressing both CCR5 and Eomes which would be associated with higher BP and greater large artery stiffness. Resting brachial BP and carotid-femoral pulse wave velocity (PWV) was measured in 10 older adults with diagnosed and treated hypertension (age: 67 ± 7 years; 5 males), 12 older adults without hypertension (age: 68 ± 8 years; 2 males) and 14 young adults (age: 22 ± 3 years; 7 males). PBMCs were isolated from whole blood and circulating T cell phenotype was determined using flow cytometry. Flow cytometry data revealed that T cells from older adults with hypertension exhibited a greater proportion of CD8+ CCR5+ Eomes hi T cells (54.68 ± 12.6%) compared to older adults without hypertension (45.70 ± 11.9%; p < 0.0161) and young adults (32.0 ± 8.6%; p < 0.0001). PWV was greater in older adults (8.1 ± 1.4 m/s; p < 0.0001) compared to young adults (5.3 ± 0.9 m/s) while there was no significant difference between the older adults with (8.2 ± 1.2 m/s; p = 0.9559) and without hypertension (8.1 ± 1.4 m/s). We found a significant positive correlation between the percentage of CD8+ CCR5+ Eomes hi T cells with PWV (R= 0.44; p < 0.0068) and mean arterial pressure (R= 0.67; p < 0.0001) in all subjects signifying a potential role of T cells in arterial stiffness and hypertension. These preliminary results provide evidence that the expansion of highly differentiated CD8+ T cells that differentially express CCR5 and Eomes are associated with arterial stiffness and hypertension in humans. This work is supported by grants from NIH R01AG086447, K01AG061271, AHA940023 (DWT) and R01 HL-127071, Moritz Chair in Geriatrics (PJF). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.