Natural killer cells, gamma delta T cells and classical monocytes are associated with systolic blood pressure in the multi-ethnic study of atherosclerosis (MESA)

Joseph A C Delaney,Susan R Heckbert,Russell P Tracy,Alan L Landay,Nels C Olson,Margaret F Doyle,Colleen M Sitlani,Bruce M Psaty,Sally A Huber,Matt Feinstein,Alison E Fohner

doi:10.1186/s12872-021-01857-2

Abstract

BackgroundHypertension is a major source of cardiovascular morbidity and mortality. Recent evidence from mouse models, genetic, and cross-sectional human studies suggest increased proportions of selected immune cell subsets may be associated with levels of systolic blood pressure (SBP).MethodsWe assayed immune cells from cryopreserved samples collected at the baseline examination (2000–2002) from 1195 participants from the multi-ethnic study of atherosclerosis (MESA). We used linear mixed models, with adjustment for age, sex, race/ethnicity, smoking, exercise, body mass index, education, diabetes, and cytomegalovirus titers, to estimate the associations between 30 immune cell subsets (4 of which were a priori hypotheses) and repeated measures of SBP (baseline and up to four follow-up measures) over 10 years. The analysis provides estimates of the association with blood pressure level.ResultsThe mean age of the MESA participants at baseline was 64 ± 10 years and 53% were male. A one standard deviation (1-SD) increment in the proportion of γδ T cells was associated with 2.40 mmHg [95% confidence interval (CI) 1.34–3.42] higher average systolic blood pressure; and for natural killer cells, a 1-SD increment was associated with 1.88 mmHg (95% CI 0.82–2.94) higher average level of systolic blood pressure. A 1-SD increment in classical monocytes (CD14++CD16−) was associated with 2.01 mmHG (95% CI 0.79–3.24) lower average systolic blood pressure. There were no associations of CD4+ T helper cell subsets with average systolic blood pressure.ConclusionThese findings suggest that the innate immune system plays a role in levels of SBP whereas there were no associations with adaptive immune cells.

Highlights

Hypertension is a major source of cardiovascular morbidity and mortality
One of our a priori hypotheses, the association between higher proportions of γδ T cells and higher systolic blood pressure replicates the association seen in Caillon et al [3] and further builds evidence that these cells are involved in the development of human hypertension. γδ T cells respond rapidly in the initiation phase of immune reactions and act as a “bridge” between the innate and adaptive systems [20]
The current data are consistent with animal models of hypertension where γδ T cell receptor gene deletion or addition of inhibitory γδ T cell receptor antibodies blunted endothelial dysfunction and hypertension in an angiotensin II model of hypertension in mice [3]. γδ T cells produce the cytokine IL-17 that has been implicated in hypertension [6, 21,22,23,24,25]

Summary

Introduction

Hypertension is a major source of cardiovascular morbidity and mortality. Recent evidence from mouse models, genetic, and cross-sectional human studies suggest increased proportions of selected immune cell subsets may be associated with levels of systolic blood pressure (SBP). Human and animal studies suggest that both the innate and adaptive immune system may be related to hypertension [3,4,5,6,7] samples sizes have been limited. This link between immune cells and hypertension may help. Investigators found that naive and memory CD4+ T cells, and T helper type 1 (Th1) cells, analyzed as proportions of CD4+ cells, were associated with subclinical atherosclerosis [8, 9] These fresh lymphocytes were from a subset of participants, at a later exam, and fewer white-cell subsets were measured in this prior study

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Conclusion