Cytomegalovirus-specific CD8+ T-cell responses are associated with arterial blood pressure in people living with HIV

Abstract

People living with HIV (PLHIV) are at increased risk for cardiovascular disease (CVD), and immunity against cytomegalovirus (CMV) may be a contributing factor. We hypothesized that enhanced T-cell responses against CMV and CMV-IgG antibody-levels are associated with higher arterial blood pressure in PLHIV. We assessed serum CMV-IgG, systolic-(SBP) and diastolic-(DBP) blood pressure, pulse pressure (PP), traditional risk factors, activated CD8+ T-cells (CD38+HLA-DR+), senescent CD8+ T-cells (CD28-CD57+) and interleukin-6 (IL-6) in 60 PLHIV and 31 HIV-uninfected controls matched on age, gender, education and comorbidity. In PLHIV, expression of interleukin-2, tumor necrosis factor-α and interferon-γ was measured by intracellular-cytokine-staining after stimulation of T-cells with CMV-pp65 and CMV-gB. Associations between CMV-specific immune responses and hypertension, SBP, DBP or PP were assessed by multivariate logistic and linear regression models adjusted for appropriate confounders. The median age of PLHIV was 47 years and 90% were male. Prevalence of hypertension in PLHIV was 37% compared to 55% of HIV-uninfected controls. CMV-specific CD8+ T-cell responses were independently associated with higher PP (CMV-pp65; β = 2.29, p = 0.001, CMV-gB; β = 2.42, p = 0.001) in PLHIV. No significant differences were found with regard to individual measures of SBP and DBP. A possible weak association was found between CMV-IgG and hypertension (β = 1.33, p = 0.049) after adjustment for age, smoking and LDL-cholesterol. HIV-related factors, IL-6, CD8+ Tcell activation or CD8+ T-cell senescence did not mediate the associations, and no associations were found between CMV-specific CD4+ T-cell responses and blood pressure in PLHIV. In conclusion, increased arterial blood pressure in PLHIV may be affected by heightened CMV-specific CD8+ T-cell responses.

Immunosenescence in atherosclerosis: A role for chronic viral infections

“…The associations between age-related telomere shortening and CAD as well as CVD-related mortality have already been investigated ( 255 – 257 ). In addition, structural alterations in biologically ageing arteries such as elastin fragmentation ( 258 ), collagen accumulation ( 259 ), decreased vascular compliance ( 260 ) and increased arterial stiffness ( 261 ) as well as elevated blood pressure ( 262 ) are reported as the consequence of chronic viral infections, too. Premature ageing may impose similar risks of developing CVDs in younger individuals.…”

The use of RNA-based treatments in the field of cancer immunotherapy

“…Moreover, Immunomic Therapeutics is collaborating with Dr. Duane Mitchell at the University of Florida on a Phase II proof of concept study using a pp65-lysosomal-associated membrane protein (LAMP)-based mRNA DC vaccine to treat patients bearing glioblastoma [730]. pp65 is a major cytomegalovirus (CMV) protein that provides exceptional tumor specificity for glioblastoma and is designed to stimulate pp65-specific CD4 + and CD8 + T cell response [731]. The previous phase I study showed a median overall survival of 35 months and progression-free survival of 31 months [731].…”

“…pp65 is a major cytomegalovirus (CMV) protein that provides exceptional tumor specificity for glioblastoma and is designed to stimulate pp65-specific CD4 + and CD8 + T cell response [731]. The previous phase I study showed a median overall survival of 35 months and progression-free survival of 31 months [731]. Table 13 highlights the different types of mRNA vaccines encoding tumor-associated antigens (TAAs) and their respective properties.…”