Abstract
BackgroundAdaptive immunity has been implicated in atherosclerosis in animal models and small clinical studies. Whether chronic immune activation is associated with atherosclerosis in otherwise healthy individuals remains underexplored. We hypothesized that activation of adaptive immune responses, as reflected by higher proportions of circulating CD4+ memory cells and lower proportions of naive cells, would be associated with subclinical atherosclerosis.Methods and FindingsWe examined cross-sectional relationships of circulating CD4+ naive and memory T cells with biomarkers of inflammation, serologies, and subclinical atherosclerosis in 912 participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Circulating CD4+ naive cells were higher in women than men and decreased with age (all p-values <0.0001). European-Americans had higher levels of naive cells and lower levels of memory cells compared with African-Americans and Hispanic-Americans (all p-values ≤0.0005). Lower naive/higher memory cells were associated with interleukin-6 levels. In multivariate models, cytomegalovirus (CMV) and H. Pylori titers were strongly associated with higher memory and lower naive cells (all p-values <0.05). Higher memory cells were associated with coronary artery calcification (CAC) level in the overall population [β-Coefficient (95% confidence interval (CI)) = 0.20 (0.03, 0.37)]. Memory and naive (inversely) cells were associated with common carotid artery intimal media thickness (CC IMT) in European-Americans [memory: β = 0.02 (0.006, 0.04); naive: β = −0.02 (−0.004, −0.03)].ConclusionsThese results demonstrate that the degree of chronic adaptive immune activation is associated with both CAC and CC IMT in otherwise healthy individuals, consistent with the known role of CD4+ T cells, and with innate immunity (inflammation), in atherosclerosis. These data are also consistent with the hypothesis that immunosenescence accelerates chronic diseases by putting a greater burden on the innate immune system, and suggest the importance of prospective studies and research into strategies to modulate adaptive immune activation in chronic disease states such as atherosclerosis.
Highlights
Clinical, animal model, and epidemiologic research have established roles for activation of innate and adaptive immune responses in atherosclerotic disease [1]
These results demonstrate that the degree of chronic adaptive immune activation is associated with both CAC and common carotid artery intimal media thickness (CC intimal media thickness (IMT)) in otherwise healthy individuals, consistent with the known role of CD4+ T cells, and with innate immunity, in atherosclerosis
These data are consistent with the hypothesis that immunosenescence accelerates chronic diseases by putting a greater burden on the innate immune system, and suggest the importance of prospective studies and research into strategies to modulate adaptive immune activation in chronic disease states such as atherosclerosis
Summary
Animal model, and epidemiologic research have established roles for activation of innate and adaptive immune responses in atherosclerotic disease [1]. In population-based epidemiological studies, increased counts of circulating leukocytes have been associated with subclinical atherosclerosis [3,4,5,6], and monocyte-derived macrophages and smooth muscle cells are characteristic throughout the atherosclerotic plaque in small-scale clinical studies [7,8]. Activation of adaptive immune responses have been implicated in atherogenesis [1]. These responses are initiated upon the recognition of cognate antigen by naive T cells. We hypothesized that activation of adaptive immune responses, as reflected by higher proportions of circulating CD4+ memory cells and lower proportions of naive cells, would be associated with subclinical atherosclerosis
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