Associations of circulating T cell subsets with endothelial function: the Multi-Ethnic Study of Atherosclerosis

Endothelial dysfunction has emerged as a risk factor for many age-related diseases such as cardiovascular disease and Alzheimer's disease and related dementias. T-lymphocytes (T cells) have been identified as important regulators of endothelial function in multiple murine models, and proinflammatory and senescent T cell subsets have been associated with endothelial dysfunction in middle-aged adults with hypertension. However, there is little data on the relationships between T cell subsets and endothelial function in large, multi-ethnic, population-based cohorts free from cardiovascular diseases. Therefore, the purpose of this study was to determine whether T cell subsets were associated with endothelial function in participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Endothelial function was assessed using flow-mediated dilation (FMD) of the brachial artery by duplex ultrasound at the baseline examination. Baseline peripheral blood T cell subsets were measured using flow cytometry (n = 968). Two analyses were used. The primary analysis examined associations of Th1 [CD4⁺ interferon-γ⁺ (IFN-γ⁺)] and CD4⁺CD28^-CD57⁺ T cells, specified as a priori hypotheses, with FMD using multivariable linear regression. Secondary analyses examined associations between 27 additional immune cell populations with FMD. Th1 and CD4⁺CD28^-CD57⁺ T cells were not associated with FMD. In secondary analyses, a 1-SD higher value of pan CD4⁺ and pan CD8⁺ T cells were associated with lower and higher FMD, respectively. These results may suggest regulation of endothelial function by T cells in preclinical models is conserved in humans. The findings warrant additional longitudinal human studies with greater T-cell phenotyping to further understand the influence of CD4⁺ and CD8⁺ T cell balance on endothelial function.NEW & NOTEWORTHY We investigated whether peripheral T cells were associated with endothelial function in a multi-ethnic cohort. No significant associations were observed between Th1 or CD4⁺CD28-CD57⁺ T cells with endothelial function in the primarily analysis. A higher value of pan CD4⁺ T cells was associated with lower endothelial function, while a higher value of pan CD8⁺ T cells was associated with higher endothelial function in the secondary analysis. This study provides epidemiological data linking pan T cells to measures of endothelial function.