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Abstract: Objectives: HIV disease is associated with increased arterial stiffness, which may be related to inflammation provoked by HIV-related immune perturbation. We assessed the association of T cell markers of immune activation and immunosenescence with carotid artery stiffness among HIV-infected women. Methods: Among 114 HIV-infected and 43 HIV-uninfected women, we measured CD4+ and CD8+ T cell populations expressing activation (CD38+HLA-DR+) and senescence (CD28-CD57+) markers. We then related these measures of immune status with parameters of carotid artery stiffness, including decreased distensibility, and increased Young''s elastic modulus, as assessed by B-mode ultrasound. Results: HIV infection was associated with increased CD4+ T cell activation, CD8+ T cell activation and CD8+ T cell senescence. Among HIV-infected women, adjusted for age, HIV medications, and vascular risk factors, higher CD4+CD38+HLA-DR+ T cell frequency was associated with decreased carotid artery distensibility (β =−2.00, 95% confidence interval [CI]=−3.86, −0.14, P =0.04) and increased Young''s modulus (β =1.00, 95% CI=0.03, 1.97, P =0.04). These associations were affected little by further adjustment for CD4+ T cell count and viral load. Among HIV-infected women, higher frequencies of immunosenescent T cells, including CD4+CD28-CD57+ and CD8+CD28-CD57+ T cells, were also associated with decreased arterial distensibility. Among HIV-uninfected women, frequencies of activated or senescent T cells were not significantly associated with measures of carotid stiffness. Discussion: T cell activation and senescence are associated with arterial stiffness, suggesting that pro-inflammatory populations of T cells may produce functional or structural vascular changes in HIV-infected women. [Copyright &y& Elsevier]

Cell-mediated immunity is implicated in atherosclerosis. We evaluated whether innate and adaptive immune cell subsets in peripheral blood are risk factors for coronary heart disease. A nested case-cohort study (n = 2155) was performed within the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS). Cases of incident myocardial infarction (MI) and incident angina (n = 880 total cases) were compared with a cohort random sample (n = 1275). Immune cell phenotypes (n = 34, including CD14+ monocytes, natural killer cells, γδ T cells, CD4+, CD8+ and CD19+ lymphocyte subsets) were measured from cryopreserved cells by flow cytometry. Cox proportional hazards models with adjustment for cardiovascular disease risk factors were used to evaluate associations of cell phenotypes with incident MI and a composite phenotype of incident MI or incident angina (MI-angina) over a median 9.3 years of follow-up. Th1, Th2, Th17, T regulatory (CD4+CD25+CD127-), naive (CD4+CD45RA+), memory (CD4+CD45RO+), and CD4+CD28− cells were specified as primary hypotheses. In secondary analyses, 27 additional cell phenotypes were investigated. After correction for multiple testing, there were no statistically significant associations of CD4+ naive, memory, CD28−, or T helper cell subsets with MI or MI-angina in MESA, CHS, or combined-cohort meta analyses. Null associations were also observed for monocyte subsets, natural killer cells, γδ T cells, CD19+ B cell and differentiated CD4+ and CD8+ cell subsets. The proportions of peripheral blood monocyte and lymphocyte subsets are not strongly related to the future occurrence of MI or angina in adults free of autoimmune disease. Image 1 • Cell-mediated immunity is established in animal models of atherosclerosis. • Unclear if immune cell levels in blood are risk factors for future coronary events. • CD4+ and CD8+ T cells were not related to incident myocardial infarction or angina. • Monocytes, innate lymphocytes, and B cells were not related to coronary risk. • Blood lymphocytes and monocytes may have limited utility as cardiovascular disease (CVD) biomarkers. [ABSTRACT FROM AUTHOR]