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

Abstract

Background: 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 pro-inflammatory 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). Methods: Endothelial function was assessed using flow-mediated dilation (FMD) of the brachial artery by duplex ultrasound at the baseline exam. Baseline peripheral blood T-cell subsets were measured using flow cytometry (N=968). Two analyses were employed. 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. Results: 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. Conclusions: These results may suggest regulation of endothelial function by T-cells in pre-clinical 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.